Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
March-2018 Volume 15 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2018 Volume 15 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review)

  • Authors:
    • Guoan Zhang
    • Meng Wang
    • Hongli Zhao
    • Wen Cui
  • View Affiliations / Copyright

    Affiliations: Cancer Pathology Research Institute, Jining Medical University, Jining, Shandong 272067, P.R. China, Department of Oncology, Shandong Jining First People's Hospital, Jining, Shandong 272111, P.R. China, Department of Gastroenterology, Shandong Control Center for Digestive Diseases, Jining, Shandong 272033, P.R. China
  • Pages: 2726-2734
    |
    Published online on: December 27, 2017
       https://doi.org/10.3892/ol.2017.7694
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Axl receptor tyrosine kinase (hereafter Axl) is a member of the tyrosine‑protein kinase receptor Tyro3, Axl and proto‑oncogene tyrosine‑protein kinase Mer family of receptor tyrosine kinases, possessing multiple different functions in normal cells. Axl is overexpressed and activated in numerous different human cancer types, triggering several signaling pathways and enhancing tumor progression. The present review assesses previous studies on the function of Axl in non‑small cell lung cancer (NSCLC). Axl is overexpressed in the tumor tissues of a number of patients with NSCLC and is associated with poorer clinical outcomes; it promotes NSCLC tumor growth, invasion/metastasis, drug resistance and the epithelial‑mesenchymal transition, thus providing a survival advantage to tumor cells. Therefore, Axl may be a promising target in NSCLC treatment.
View Figures

Figure 1

View References

1 

Linger RM, Keating AK, Earp HS and Graham DK: TAM receptor tyrosine kinases: Biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res. 100:35–83. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Lemmon MA and Schlessinger J: Cell signaling by receptor tyrosine kinases. Cell. 141:1117–1134. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Graham DK, DeRyckere D, Davies KD and Earp HS: The TAM family: Phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer. 14:769–785. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Rothlin CV, Carrera-Silva EA, Bosurgi L and Ghosh S: TAM receptor signaling in immune homeostasis. Annu Rev Immunol. 33:355–391. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Lemke G and Rothlin CV: Immunobiology of the TAM receptors. Nat Rev Immunol. 8:327–336. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Stitt TN, Conn G, Gore M, Lai C, Bruno J, Radziejewski C, Mattsson K, Fisher J, Gies DR, Jones PF, et al: The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell. 80:661–670. 1995. View Article : Google Scholar : PubMed/NCBI

7 

Varnum BC, Young C, Elliott G, Garcia A, Bartley TD, Fridell YW, Hunt RW, Trail G, Clogston C, Toso RJ, et al: Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6. Nature. 373:623–626. 1995. View Article : Google Scholar : PubMed/NCBI

8 

Manfioletti G, Brancolini C, Avanzi G and Schneider C: The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol. 13:4976–4985. 1993. View Article : Google Scholar : PubMed/NCBI

9 

Caberoy NB, Alvarado G, Bigcas JL and Li W: Galectin-3 is a new MerTK-specific eat-me signal. J Cell Physiol. 227:401–407. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Caberoy NB, Zhou Y and Li W: Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J. 29:3898–3910. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Verma A, Warner SL, Vankayalapati H, Bearss DJ and Sharma S: Targeting Axl and Mer kinases in cancer. Mol Cancer Ther. 10:1763–1773. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Liu E, Hjelle B and Bishop JM: Transforming genes in chronic myelogenous leukemia. Proc Natl Acad Sci USA. 85:pp. 1952–1956. 1988; View Article : Google Scholar : PubMed/NCBI

13 

O'Bryan JP, Frye RA, Cogswell PC, Neubauer A, Kitch B, Prokop C, Espinosa R III, Le Beau MM, Earp HS and Liu ET: axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol Cell Biol. 11:5016–5031. 1991. View Article : Google Scholar : PubMed/NCBI

14 

Janssen JW, Schulz AS, Steenvoorden AC, Schmidberger M, Strehl S, Ambros PF and Bartram CR: A novel putative tyrosine kinase receptor with oncogenic potential. Oncogene. 6:2113–2120. 1991.PubMed/NCBI

15 

O'Bryan JP, Fridell YW, Koski R, Varnum B and Liu ET: The transforming receptor tyrosine kinase, Axl, is post-translationally regulated by proteolytic cleavage. J Biol Chem. 270:551–557. 1995. View Article : Google Scholar : PubMed/NCBI

16 

Reichl P, Fang M, Starlinger P, Staufer K, Nenutil R, Muller P, Greplova K, Valik D, Dooley S, Brostjan C, et al: Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma. Int J Cancer. 137:385–394. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Hafizi S and Dahlbäck B: Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev. 17:295–304. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Chung BI, Malkowicz SB, Nguyen TB, Libertino JA and McGarvey TW: Expression of the proto-oncogene Axl in renal cell carcinoma. DNA Cell Biol. 22:533–540. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Prieto AL, Weber JL and Lai C: Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and mer in the developing rat central nervous system. J Comp Neurol. 425:295–314. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Lafdil F, Chobert MN, Couchie D, Brouillet A, Zafrani ES, Mavier P and Laperche Y: Induction of Gas6 protein in CCl4-induced rat liver injury and anti-apoptotic effect on hepatic stellate cells. Hepatology. 44:228–239. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Melaragno MG, Fridell YW and Berk BC: The Gas6/Axl system: A novel regulator of vascular cell function. Trends Cardiovasc Med. 9:250–253. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Ruan GX and Kazlauskas A: Axl is essential for VEGF-A-dependent activation of PI3K/Akt. EMBO J. 31:1692–1703. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Neubauer A, Fiebeler A, Graham DK, O'Bryan JP, Schmidt CA, Barckow P, Serke S, Siegert W, Snodgrass HR, Huhn D, et al: Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis. Blood. 84:1931–1941. 1994.PubMed/NCBI

24 

Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F, Arnout J, Dewerchin M, Hoylaerts M, Herbert J, et al: Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med. 7:215–221. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H and Mizuno K: Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem. 271:30022–30027. 1996. View Article : Google Scholar : PubMed/NCBI

26 

Schneider C, King RM and Philipson L: Genes specifically expressed at growth arrest of mammalian cells. Cell. 54:787–793. 1988. View Article : Google Scholar : PubMed/NCBI

27 

Laurance S, Lemarié CA and Blostein MD: Growth Arrest-specific gene 6 (gas6) and vascular hemostasis. Adv Nutr. 3:196–203. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Hafizi S and Dahlbäck B: Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. FEBS J. 273:5231–5244. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Sasaki T, Knyazev PG, Clout NJ, Cheburkin Y, Göhring W, Ullrich A, Timpl R and Hohenester E: Structural basis for Gas6-Axl signalling. EMBO J. 25:80–87. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Tsou WI, Nguyen KQ, Calarese DA, Garforth SJ, Antes AL, Smirnov SV, Almo SC, Birge RB and Kotenko SV: Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and complex regulation of ligand-induced activation. J Biol Chem. 289:25750–25763. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Lew ED, Oh J, Burrola PG, Lax I, Zagórska A, Través PG, Schlessinger J and Lemke G: Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. Elife. 3:2014. View Article : Google Scholar : PubMed/NCBI

32 

Meyer AS, Miller MA, Gertler FB and Lauffenburger DA: The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells. Sci Signal. 6:ra662013. View Article : Google Scholar : PubMed/NCBI

33 

Brand TM, Iida M, Stein AP, Corrigan KL, Braverman CM, Luthar N, Toulany M, Gill PS, Salgia R, Kimple RJ and Wheeler DL: AXL mediates resistance to cetuximab therapy. Cancer Res. 74:5152–5164. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Elkabets M, Pazarentzos E, Juric D, Sheng Q, Pelossof RA, Brook S, Benzaken AO, Rodon J, Morse N, Yan JJ, et al: AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas. Cancer Cell. 27:533–546. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Fridell YW, Jin Y, Quilliam LA, Burchert A, McCloskey P, Spizz G, Varnum B, Der C and Liu ET: Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase. Mol Cell Biol. 16:135–145. 1996. View Article : Google Scholar : PubMed/NCBI

36 

Braunger J, Schleithoff L, Schulz AS, Kessler H, Lammers R, Ullrich A, Bartram CR and Janssen JW: Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene. 14:2619–2631. 1997. View Article : Google Scholar : PubMed/NCBI

37 

Abu-Thuraia A, Gauthier R, Chidiac R, Fukui Y, Screaton RA, Gratton JP and Côté JF: Axl phosphorylates elmo scaffold proteins to promote Rac activation and cell invasion. Mol Cell Biol. 35:76–87. 2015. View Article : Google Scholar : PubMed/NCBI

38 

Linger RM, Keating AK, Earp HS and Graham DK: Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors. Expert Opin Ther Targets. 14:1073–1090. 2010. View Article : Google Scholar : PubMed/NCBI

39 

Yanagita M, Arai H, Nakano T, Ohashi K, Mizuno K, Fukatsu A, Doi T and Kita T: Gas6 induces mesangial cell proliferation via latent transcription factor STAT3. J Biol Chem. 276:42364–42369. 2001. View Article : Google Scholar : PubMed/NCBI

40 

Brandão L, Migdall-Wilson J, Eisenman K and Graham DK: TAM receptors in leukemia: Expression, signaling, and therapeutic implications. Crit Rev Oncog. 16:47–63. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Linger RM, Cohen RA, Cummings CT, Sather S, Migdall-Wilson J, Middleton DH, Lu X, Barón AE, Franklin WA, Merrick DT, et al: Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer. Oncogene. 32:3420–3431. 2013. View Article : Google Scholar : PubMed/NCBI

42 

Iida S, Miki Y, Suzuki T, Mori K, Saito M, Niikawa H, Kondo T, Yamada-Okabe H and Sasano H: Activation of AXL and antitumor effects of a monoclonal antibody to AXL in lung adenocarcinoma. Anticancer Res. 34:1821–1827. 2014.PubMed/NCBI

43 

Fujimori T, Grabiec AM, Kaur M, Bell TJ, Fujino N, Cook PC, Svedberg FR, MacDonald AS, Maciewicz RA, Singh D and Hussell T: The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung. Mucosal Immunol. 8:1021–1030. 2015. View Article : Google Scholar : PubMed/NCBI

44 

Schmid ET, Pang IK, Carrera Silva EA, Bosurgi L, Miner JJ, Diamond MS, Iwasaki A and Rothlin CV: AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity. Elife. 5:pii: e124142016. View Article : Google Scholar

45 

Healy AM, Schwartz JJ, Zhu X, Herrick BE, Varnum B and Farber HW: Gas 6 promotes Axl-mediated survival in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol. 280:L1273–L1281. 2001. View Article : Google Scholar : PubMed/NCBI

46 

Wang Y, Xia H, Zhuang Z, Miao L, Chen X and Cai H: Axl-altered microRNAs regulate tumorigenicity and gefitinib resistance in lung cancer. Cell Death Dis. 5:e12272014. View Article : Google Scholar : PubMed/NCBI

47 

Wu F, Li J, Jang C, Wang J and Xiong J: The role of Axl in drug resistance and epithelial-to-mesenchymal transition of non-small cell lung carcinoma. Int J Clin Exp Pathol. 7:6653–6661. 2014.PubMed/NCBI

48 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

49 

Wilson C, Ye X, Pham T, Lin E, Chan S, McNamara E, Neve RM, Belmont L, Koeppen H, Yauch RL, et al: AXL inhibition sensitizes mesenchymal cancer cells to antimitotic drugs. Cancer Res. 74:5878–5890. 2014. View Article : Google Scholar : PubMed/NCBI

50 

Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, et al: An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res. 19:279–290. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI

52 

Ishikawa M, Sonobe M, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N and Date H: Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients. Ann Surg Oncol. 20 Suppl 3:S467–S476. 2013. View Article : Google Scholar : PubMed/NCBI

53 

Shieh YS, Lai CY, Kao YR, Shiah SG, Chu YW, Lee HS and Wu CW: Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia. 7:1058–1064. 2005. View Article : Google Scholar : PubMed/NCBI

54 

Wu Z, Bai F, Fan L, Pang W, Han R, Wang J, Liu Y, Yan X, Duan H and Xing L: Coexpression of receptor tyrosine kinase AXL and EGFR in human primary lung adenocarcinomas. Hum Pathol. 46:1935–1944. 2015. View Article : Google Scholar : PubMed/NCBI

55 

Kurokawa M, Ise N, Omi K, Goishi K and Higashiyama S: Cisplatin influences acquisition of resistance to molecular-targeted agents through epithelial-mesenchymal transition-like changes. Cancer Sci. 104:904–911. 2013. View Article : Google Scholar : PubMed/NCBI

56 

Lay JD, Hong CC, Huang JS, Yang YY, Pao CY, Liu CH, Lai YP, Lai GM, Cheng AL, Su IJ and Chuang SE: Sulfasalazine suppresses drug resistance and invasiveness of lung adenocarcinoma cells expressing AXL. Cancer Res. 67:3878–3887. 2007. View Article : Google Scholar : PubMed/NCBI

57 

Huang JS, Cho CY, Hong CC, Yan MD, Hsieh MC, Lay JD, Lai GM, Cheng AL and Chuang SE: Oxidative stress enhances AXL-mediated cell migration through AKT1/Rac1-dependent mechanism. Free Radic Biol Med. 65:1246–1256. 2013. View Article : Google Scholar : PubMed/NCBI

58 

Tai KY, Shieh YS, Lee CS, Shiah SG and Wu CW: Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-kappaB and Brg-1. Oncogene. 27:4044–4055. 2008. View Article : Google Scholar : PubMed/NCBI

59 

Reichl P, Dengler M, van Zijl F, Huber H, Führlinger G, Reichel C, Sieghart W, Peck-Radosavljevic M, Grubinger M and Mikulits W: Axl activates autocrine transforming growth factor-β signaling in hepatocellular carcinoma. Hepatology. 61:930–941. 2015. View Article : Google Scholar : PubMed/NCBI

60 

Chiu KC, Lee CH, Liu SY, Yeh CT, Huang RY, Yuh DY, Cheng JC, Chou YT and Shieh YS: Protumoral effect of macrophage through Axl activation on mucoepidermoid carcinoma. J Oral Pathol Med. 43:538–544. 2014. View Article : Google Scholar : PubMed/NCBI

61 

Han J, Tian R, Yong B, Luo C, Tan P, Shen J and Peng T: Gas6/Axl mediates tumor cell apoptosis, migration and invasion and predicts the clinical outcome of osteosarcoma patients. Biochem Biophys Res Commun. 435:493–500. 2013. View Article : Google Scholar : PubMed/NCBI

62 

Asiedu MK, Beauchamp-Perez FD, Ingle JN, Behrens MD, Radisky DC and Knutson KL: AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells. Oncogene. 33:1316–1324. 2014. View Article : Google Scholar : PubMed/NCBI

63 

Cheng P, Phillips E, Kim SH, Taylor D, Hielscher T, Puccio L, Hjelmeland AB, Lichter P, Nakano I and Goidts V: Kinome-wide shRNA screen identifies the receptor tyrosine kinase AXL as a key regulator for mesenchymal glioblastoma stem-like cells. Stem Cell Reports. 4:899–913. 2015. View Article : Google Scholar : PubMed/NCBI

64 

Allen MP, Linseman DA, Udo H, Xu M, Schaack JB, Varnum B, Kandel ER, Heidenreich KA and Wierman ME: Novel mechanism for gonadotropin-releasing hormone neuronal migration involving Gas6/Ark signaling to p38 mitogen-activated protein kinase. Mol Cell Biol. 22:599–613. 2002. View Article : Google Scholar : PubMed/NCBI

65 

Mahadevan D, Cooke L, Riley C, Swart R, Simons B, Della Croce K, Wisner L, Iorio M, Shakalya K, Garewal H, et al: A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene. 26:3909–3919. 2007. View Article : Google Scholar : PubMed/NCBI

66 

Giles KM, Kalinowski FC, Candy PA, Epis MR, Zhang PM, Redfern AD, Stuart LM, Goodall GJ and Leedman PJ: Axl mediates acquired resistance of head and neck cancer cells to the epidermal growth factor receptor inhibitor erlotinib. Mol Cancer Ther. 12:2541–2558. 2013. View Article : Google Scholar : PubMed/NCBI

67 

Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R, Halsey W, Sathe GM, Martin AM and Gilmer TM: Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: Activation of AXL. Cancer Res. 69:6871–6878. 2009. View Article : Google Scholar : PubMed/NCBI

68 

Paccez JD, Vogelsang M, Parker MI and Zerbini LF: The receptor tyrosine kinase Axl in cancer: Biological functions and therapeutic implications. Int J Cancer. 134:1024–1033. 2014. View Article : Google Scholar : PubMed/NCBI

69 

Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFramboise T, Abdel-Rahman M, Wang X, Levine AD, Rho JK, et al: Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 44:852–860. 2012. View Article : Google Scholar : PubMed/NCBI

70 

Ji W, Choi CM, Rho JK, Jang SJ, Park YS, Chun SM, Kim WS, Lee JS, Kim SW, Lee DH and Lee JC: Mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitor in Korean patients with lung cancer. BMC Cancer. 13:6062013. View Article : Google Scholar : PubMed/NCBI

71 

Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS and Kalluri R: Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 527:525–530. 2015. View Article : Google Scholar : PubMed/NCBI

72 

Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, et al: Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 527:472–476. 2015. View Article : Google Scholar : PubMed/NCBI

73 

Lee WP, Wen Y, Varnum B and Hung MC: Akt is required for Axl-Gas6 signaling to protect cells from E1A-mediated apoptosis. Oncogene. 21:329–336. 2002. View Article : Google Scholar : PubMed/NCBI

74 

Papadakis ES, Cichoń MA, Vyas JJ, Patel N, Ghali L, Cerio R, Storey A and O'Toole EA: Axl promotes cutaneous squamous cell carcinoma survival through negative regulation of pro-apoptotic Bcl-2 family members. J Invest Dermatol. 131:509–517. 2011. View Article : Google Scholar : PubMed/NCBI

75 

Hong CC, Lay JD, Huang JS, Cheng AL, Tang JL, Lin MT, Lai GM and Chuang SE: Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia. Cancer Lett. 268:314–324. 2008. View Article : Google Scholar : PubMed/NCBI

76 

Meric-Bernstam F and Gonzalez-Angulo AM: Targeting the mTOR signaling network for cancer therapy. J Clin Oncol. 27:2278–2287. 2009. View Article : Google Scholar : PubMed/NCBI

77 

Suda K, Mizuuchi H, Sato K, Takemoto T, Iwasaki T and Mitsudomi T: The insulin-like growth factor 1 receptor causes acquired resistance to erlotinib in lung cancer cells with the wild-type epidermal growth factor receptor. Int J Cancer. 135:1002–1006. 2014. View Article : Google Scholar : PubMed/NCBI

78 

Myers SH, Brunton VG and Unciti-Broceta A: AXL inhibitors in cancer: A medicinal chemistry perspective. J Med Chem. 59:3593–3608. 2016. View Article : Google Scholar : PubMed/NCBI

79 

Feneyrolles C, Spenlinhauer A, Guiet L, Fauvel B, Daydé-Cazals B, Warnault P, Chevé G and Yasri A: Axl kinase as a key target for oncology: Focus on small molecule inhibitors. Mol Cancer Ther. 13:2141–2148. 2014. View Article : Google Scholar : PubMed/NCBI

80 

Levin PA, Brekken RA, Byers LA, Heymach JV and Gerber DE: Axl receptor axis: A new therapeutic target in lung cancer. J Thorac Oncol. 11:1357–1362. 2016. View Article : Google Scholar : PubMed/NCBI

81 

Wu X, Liu X, Koul S, Lee CY, Zhang Z and Halmos B: AXL kinase as a novel target for cancer therapy. Oncotarget. 5:9546–9563. 2014. View Article : Google Scholar : PubMed/NCBI

82 

Holland SJ, Pan A, Franci C, Hu Y, Chang B, Li W, Duan M, Torneros A, Yu J, Heckrodt TJ, et al: R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res. 70:1544–1554. 2010. View Article : Google Scholar : PubMed/NCBI

83 

Sheridan C: First Axl inhibitor enters clinical trials. Nat Biotechnol. 31:775–776. 2013. View Article : Google Scholar : PubMed/NCBI

84 

Nimmagadda S, Pullambhatla M, Lisok A, Hu C, Maitra A and Pomper MG: Imaging Axl expression in pancreatic and prostate cancer xenografts. Biochem Biophys Res Commun. 443:635–640. 2014. View Article : Google Scholar : PubMed/NCBI

85 

Qu XH, Liu JL, Zhong XW, Li XI and Zhang QG: Insights into the roles of hnRNP A2/B1 and AXL in non-small cell lung cancer. Oncol Lett. 10:1677–1685. 2015. View Article : Google Scholar : PubMed/NCBI

86 

Choi YJ, Kim SY, So KS, Baek IJ, Kim WS, Choi SH, Lee JC, Bivona TG, Rho JK and Choi CM: AUY922 effectively overcomes MET- and AXL-mediated resistance to EGFR-TKI in lung cancer cells. PLoS One. 10:e01198322015. View Article : Google Scholar : PubMed/NCBI

87 

Bae SY, Hong JY, Lee HJ, Park HJ and Lee SK: Targeting the degradation of AXL receptor tyrosine kinase to overcome resistance in gefitinib-resistant non-small cell lung cancer. Oncotarget. 6:10146–10160. 2015. View Article : Google Scholar : PubMed/NCBI

88 

Yoshida T, Zhang G, Smith MA, Lopez AS, Bai Y, Li J, Fang B, Koomen J, Rawal B, Fisher KJ, et al: Tyrosine phosphoproteomics identifies both codrivers and cotargeting strategies for T790M-related EGFR-TKI resistance in non-small cell lung cancer. Clin Cancer Res. 20:4059–4074. 2014. View Article : Google Scholar : PubMed/NCBI

89 

Kim HR, Kim WS, Choi YJ, Choi CM, Rho JK and Lee JC: Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation. Mol Oncol. 7:1093–1102. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang G, Wang M, Zhao H and Cui W: Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review). Oncol Lett 15: 2726-2734, 2018.
APA
Zhang, G., Wang, M., Zhao, H., & Cui, W. (2018). Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review). Oncology Letters, 15, 2726-2734. https://doi.org/10.3892/ol.2017.7694
MLA
Zhang, G., Wang, M., Zhao, H., Cui, W."Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review)". Oncology Letters 15.3 (2018): 2726-2734.
Chicago
Zhang, G., Wang, M., Zhao, H., Cui, W."Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review)". Oncology Letters 15, no. 3 (2018): 2726-2734. https://doi.org/10.3892/ol.2017.7694
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang G, Wang M, Zhao H and Cui W: Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review). Oncol Lett 15: 2726-2734, 2018.
APA
Zhang, G., Wang, M., Zhao, H., & Cui, W. (2018). Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review). Oncology Letters, 15, 2726-2734. https://doi.org/10.3892/ol.2017.7694
MLA
Zhang, G., Wang, M., Zhao, H., Cui, W."Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review)". Oncology Letters 15.3 (2018): 2726-2734.
Chicago
Zhang, G., Wang, M., Zhao, H., Cui, W."Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review)". Oncology Letters 15, no. 3 (2018): 2726-2734. https://doi.org/10.3892/ol.2017.7694
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team