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
November-2016 Volume 12 Issue 5

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
November-2016 Volume 12 Issue 5

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
Article Open Access

Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling

  • Authors:
    • Hong Ji
    • Bo Li
    • Shitai Zhang
    • Zheng He
    • Yang Zhou
    • Ling Ouyang
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
    Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3811-3817
    |
    Published online on: September 21, 2016
       https://doi.org/10.3892/ol.2016.5160
  • 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

Overexpression of Crk-like (CrkL) adapter protein has been implicated in a number of types of human cancer. However, its involvement in human cervical carcinoma remains unclear. The present study aimed to explore the clinical significance and biological characteristics of CrkL in human cervical carcinoma. CrkL protein expression was examined in tissue samples from 92 cases of cervical carcinoma using immunohistochemistry, and was found to be overexpressed in 48.9% (45/92 cases). CrkL was transfected into HeLa and CaSki cervical carcinoma cell lines and its effects on biological behavior were examined. CrkL overexpression was revealed to promote cell proliferation, invasion and chemoresistance. In addition, CrkL overexpression increased the level of Src and Akt phosphorylation. Treatment with the Src inhibitor dasatinib eliminated the effect of CrkL on cell invasion. In conclusion, the current results demonstrate that CrkL is an oncoprotein overexpressed in cervical carcinoma which contributes to malignant cell growth and chemoresistance. In addition, the findings indicate that CrkL promotes cervical cancer cell invasion through a Src-dependent pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Wang T, Wu MH, Wu YM and Zhang WY: A population-based study of invasive cervical cancer patients in Beijing: 1993–2008. Chin Med J (Engl). 128:3298–3304. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Angioli R, Plotti F, Luvero D, Aloisi A, Guzzo F, Capriglione S, Terranova C, De Cicco Nardone C and Benedetti-Panici P: Feasibility and safety of carboplatin plus paclitaxel as neoadjuvant chemotherapy for locally advanced cervical cancer: A pilot study. Tumour Biol. 35:2741–2746. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Organista-Nava J, Gómez-Gómez Y and Gariglio P: Embryonic stem cell-specific signature in cervical cancer. Tumour Biol. 35:1727–1738. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Du PL, Wu KS, Fang JY, Zeng Y, Xu ZX, Tang WR, Xu XL and Lin K: Cervical cancer mortality trends in China, 1991–2013, and predictions for the future. Asian Pac J Cancer Prev. 16:6391–6396. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Wentzensen N, Schwartz L, Zuna RE, Smith K, Mathews C, Gold MA, Allen RA, Zhang R, Dunn ST, Walker JL and Schiffman M: Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population. Clin Cancer Res. 18:4154–4162. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Schwarz JK, Payton JE, Rashmi R, Xiang T, Jia Y, Huettner P, Rogers BE, Yang Q, Watson M, Rader JS and Grigsby PW: Pathway-specific analysis of gene expression data identifies the PI3K/Akt pathway as a novel therapeutic target in cervical cancer. Clin Cancer Res. 18:1464–1471. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Rhodes J, York RD, Tara D, Tajinda K and Druker BJ: CrkL functions as a nuclear adaptor and transcriptional activator in Bcr-Abl-expressing cells. Exp Hematol. 28:305–310. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Feller SM: Crk family adaptors-signalling complex formation and biological roles. Oncogene. 20:6348–6371. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Fidler IJ and Kripke ML: Genomic analysis of primary tumors does not address the prevalence of metastatic cells in the population. Nat Genet. 34(23): author reply 25. 2003.PubMed/NCBI

11 

ten Hoeve J, Morris C, Heisterkamp N and Groffen J: Isolation and chromosomal localization of CRKL, a human crk-like gene. Oncogene. 8:2469–2474. 1993.PubMed/NCBI

12 

Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV and Griffin JD: Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120 (CBL). J Biol Chem. 272:10248–10253. 1997. View Article : Google Scholar : PubMed/NCBI

13 

Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD and Druker BJ: Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. J Biol Chem. 269:22925–22928. 1994.PubMed/NCBI

14 

Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, et al: The landscape of somatic copy-number alteration across human cancers. Nature. 463:899–905. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Senechal K, Halpern J and Sawyers CL: The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene. J Biol Chem. 271:23255–23261. 1996. View Article : Google Scholar : PubMed/NCBI

16 

van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 415:530–536. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Lin F, Chengyao X, Qingchang L, Qianze D, Enhua W and Yan W: CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway. Mol Carcinog. 54(Suppl 1): E35–E44. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Wang Y, Dong QZ, Fu L, Stoecker M, Wang E and Wang EH: Overexpression of CRKL correlates with poor prognosis and cell proliferation in non-small cell lung cancer. Mol Carcinog. 52:890–899. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Senechal K, Heaney C, Druker B and Sawyers CL: Structural requirements for function of the Crkl adapter protein in fibroblasts and hematopoietic cells. Mol Cell Biol. 18:5082–5090. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Schönherr C, Yang HL, Vigny M, Palmer RH and Hallberg B: Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells. Oncogene. 29:2817–2830. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Zhao T, Miao Z, Wang Z, Xu Y, Wu J, Liu X, You Y and Li J: Overexpression of CRKL correlates with malignant cell proliferation in breast cancer. Tumour Biol. 34:2891–2897. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Zhao S, Li H, Wang Q, Su C, Wang G, Song H, Zhao L, Luan Z and Su R: The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M. BMC Cancer. 15:3892015. View Article : Google Scholar : PubMed/NCBI

24 

Tamura M, Sasaki Y, Kobashi K, Takeda K, Nakagaki T, Idogawa M and Tokino T: CRKL oncogene is downregulated by p53 through miR-200s. Cancer Sci. 106:1033–1040. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Ladanyi M: CRKL as a lung cancer oncogene and mediator of acquired resistance to EGFR inhibitors: Is it all that it is cracked up to be? Cancer Discov. 1:560–561. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Koval AP, Karas M, Zick Y and LeRoith D: Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. J Biol Chem. 273:14780–14787. 1998. View Article : Google Scholar : PubMed/NCBI

27 

Fu L, Dong Q, Xie C, Wang Y and Li Q: CRKL protein overexpression enhances cell proliferation and invasion in pancreatic cancer. Tumour Biol. 36:1015–1022. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Singer CF, Hudelist G, Lamm W, Mueller R, Handl C, Kubista E and Czerwenka K: Active (p)CrkL is overexpressed in human malignancies: Potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition. Oncol Rep. 15:353–359. 2006.PubMed/NCBI

29 

Kim YH, Kwei KA, Girard L, Salari K, Kao J, Pacyna-Gengelbach M, Wang P, Hernandez-Boussard T, Gazdar AF, Petersen I, et al: Genomic and functional analysis identifies CRKL as an oncogene amplified in lung cancer. Oncogene. 29:1421–1430. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Fathers KE, Bell ES, Rajadurai CV, Cory S, Zhao H, Mourskaia A, Zuo D, Madore J, Monast A, Mes-Masson AM, et al: Crk adaptor proteins act as key signaling integrators for breast tumorigenesis. Breast Cancer Res. 14:R742012. View Article : Google Scholar : PubMed/NCBI

31 

Graf R, Barbero S, Keller N, Chen L, Uryu S, Schlaepfer D and Stupack D: Src-inducible association of CrkL with procaspase-8 promotes cell migration. Cell Adh Migr. 7:362–369. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Shen Q, Rahn JJ, Zhang J, Gunasekera N, Sun X, Shaw AR, Hendzel MJ, Hoffman P, Bernier A and Hugh JC: MUC1 initiates Src-CrkL-Rac1/Cdc42-mediated actin cytoskeletal protrusive motility after ligating intercellular adhesion molecule-1. Mol Cancer Res. 6:555–567. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Guarino M: Src signaling in cancer invasion. J Cell Physiol. 223:14–26. 2010.PubMed/NCBI

34 

Cui A, Hua H, Shao T, Song P, Kong Q, Luo T and Jiang Y: Aflatoxin B1 induces Src phosphorylation and stimulates lung cancer cell migration. Tumour Biol. 36:6507–6513. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Sun B, Yang N, Jiang Y, Zhang H, Hou C, Ji C, Liu Y and Zuo P: Antagomir-1290 suppresses CD133+ cells in non-small cell lung cancer by targeting fyn-related Src family tyrosine kinase. Tumour Biol. 36:6223–6230. 2015. View Article : Google Scholar : PubMed/NCBI

36 

Wang JH, Nao JF, Zhang M and He P: 20 (s)-ginsenoside Rg3 promotes apoptosis in human ovarian cancer HO-8910 cells through PI3K/Akt and XIAP pathways. Tumour Biol. 35:11985–11994. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Ye G, Lu Q, Zhao W, Du D, Jin L and Liu Y: Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via PI3K/Akt pathway. Tumour Biol. 35:11261–11267. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ji H, Li B, Zhang S, He Z, Zhou Y and Ouyang L: Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling. Oncol Lett 12: 3811-3817, 2016.
APA
Ji, H., Li, B., Zhang, S., He, Z., Zhou, Y., & Ouyang, L. (2016). Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling. Oncology Letters, 12, 3811-3817. https://doi.org/10.3892/ol.2016.5160
MLA
Ji, H., Li, B., Zhang, S., He, Z., Zhou, Y., Ouyang, L."Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling". Oncology Letters 12.5 (2016): 3811-3817.
Chicago
Ji, H., Li, B., Zhang, S., He, Z., Zhou, Y., Ouyang, L."Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling". Oncology Letters 12, no. 5 (2016): 3811-3817. https://doi.org/10.3892/ol.2016.5160
Copy and paste a formatted citation
x
Spandidos Publications style
Ji H, Li B, Zhang S, He Z, Zhou Y and Ouyang L: Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling. Oncol Lett 12: 3811-3817, 2016.
APA
Ji, H., Li, B., Zhang, S., He, Z., Zhou, Y., & Ouyang, L. (2016). Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling. Oncology Letters, 12, 3811-3817. https://doi.org/10.3892/ol.2016.5160
MLA
Ji, H., Li, B., Zhang, S., He, Z., Zhou, Y., Ouyang, L."Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling". Oncology Letters 12.5 (2016): 3811-3817.
Chicago
Ji, H., Li, B., Zhang, S., He, Z., Zhou, Y., Ouyang, L."Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling". Oncology Letters 12, no. 5 (2016): 3811-3817. https://doi.org/10.3892/ol.2016.5160
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