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Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma

  • Authors:
    • Sha Han
    • Yequan Wang
    • Chengyan Ge
    • Mingtao Gao
    • Xintong Wang
    • Feiyu Wang
    • Lei Sun
    • Sheng Li
    • Tingting Dong
    • Zhen Dang
    • Wen Cui
    • Guoan Zhang
    • Ning Liu
  • View Affiliations / Copyright

    Affiliations: Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China, Institute of Forensic Medicine and Laboratory Medicine, Forensic Science Center of Jining, Jining Medical University, Jining, Shandong 272067, P.R. China, The Second Medical College, Jining Medical University, Jining, Shandong 272067, P.R. China, Information Technology Centre, Jining Medical University, Jining, Shandong 272067, P.R. China
    Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 41
    |
    Published online on: September 2, 2020
       https://doi.org/10.3892/etm.2020.9169
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Abstract

Esophageal squamous cell carcinoma (ESCC) is a common type of cancer in a number of regions of the world, including East Asia, South Africa and Iran. It is often associated with poor prognosis rates. Tyrosine‑protein kinase receptor UFO (AXL) is overexpressed in a subset of ESCC tumors, therefore the present study aimed to determine the effect of R428, a selective inhibitor of AXL, on ESCC tumor cells. TE1 and KYSE150 cell lines were used as models to investigate the effects of R428 treatment. The proliferative rate of the tumor cells was analyzed using MTT and colony formation assays. In addition, cell migration and invasion rates were analyzed using wound healing and Matrigel assays, respectively. The expression levels of matrix metalloproteinase (MMP)2 and MMP9, and the activation of protein kinase B (AKT), extracellular signal‑regulated kinase (ERK) and AXL signaling were analyzed using gelatin zymography and western blotting. The results revealed that R428 inhibited the proliferative and invasive abilities of both cell lines. Furthermore, AXL, AKT and ERK signaling were all decreased in response to R428 treatment, alongside the expression levels of MMP2 and MMP9. In conclusion, the results of the present study suggested that R428 treatment may suppress ESCC tumor cell proliferation and invasion, representing a potential therapeutic target for ESCC.
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1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011.PubMed/NCBI View Article : Google Scholar

2 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016.PubMed/NCBI View Article : Google Scholar

3 

Allum WH, Stenning SP, Bancewicz J, Clark PI and Langley RE: Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 27:5062–5067. 2009.PubMed/NCBI View Article : Google Scholar

4 

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.PubMed/NCBI View Article : Google Scholar

5 

Qu X, Liu G, Zhong X, Li X and Zhang Q: Role of AXL expression in non-small cell lung cancer. Oncol Lett. 12:5085–5091. 2016.PubMed/NCBI View Article : Google Scholar

6 

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.PubMed/NCBI View Article : Google Scholar

7 

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.PubMed/NCBI View Article : Google Scholar

8 

Duan Y, Hu B, Qiao C, Luo L, Li X, Wang J, Liu H, Zhou T, Shen B, Lv M and Feng J: Engineered AXL-ECD-Fc variants that abolish the AXL/Gas6 interaction suppress tumor cell migration. Oncol Lett. 17:5784–5792. 2019.PubMed/NCBI View Article : Google Scholar

9 

Hsieh MS, Yang PW, Wong LF and Lee JM: The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma. Oncotarget. 7:36956–36970. 2016.PubMed/NCBI View Article : Google Scholar

10 

Paccez JD, Duncan K, Vava A, Correa RG, Libermann TA, Parker MI and Zerbini LF: Inactivation of GSK3β and activation of NF-κB pathway via Axl represents an important mediator of tumorigenesis in esophageal squamous cell carcinoma. Mol Biol Cell. 26:821–831. 2015.PubMed/NCBI View Article : Google Scholar

11 

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.PubMed/NCBI View Article : Google Scholar

12 

Zhang G, Kong X, Wang M, et al: AXL is a marker for epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Oncol Lett. 15:1900–1906. 2018.PubMed/NCBI View Article : Google Scholar

13 

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

14 

Wu Y, Hu L, Liang Y, Li J, Wang K, Chen X, Meng H, Guan X, Yang K and Bai Y: Up-regulation of lncRNA CASC9 promotes esophageal squamous cell carcinoma growth by negatively regulating PDCD4 expression through EZH2. Mol Cancer. 16(150)2017.PubMed/NCBI View Article : Google Scholar

15 

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.PubMed/NCBI View Article : Google Scholar

16 

Yang PW, Liu YC, Chang YH, Lin CC, Huang PM, Hua KT, Lee JM and Hsieh MS: Cabozantinib (XL184) and R428 (BGB324) inhibit the growth of esophageal squamous cell carcinoma (ESCC). Front Oncol. 9(1138)2019.PubMed/NCBI View Article : Google Scholar

17 

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(ra66)2013.PubMed/NCBI View Article : Google Scholar

18 

Hansen MB, Nielsen SE and Berg K: Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 119:203–210. 1989.PubMed/NCBI View Article : Google Scholar

19 

Kong LL, Man DM, Wang T, Zhang GA and Cui W: siRNA targeting RBP2 inhibits expression, proliferation, tumorigenicity and invasion in thyroid carcinoma cells. Oncol Lett. 10:3393–3398. 2015.PubMed/NCBI View Article : Google Scholar

20 

Tang Z, Yang L, Wang Y, Xue R, Zhang J, Huang W, Chen PC and Sung KL: Contributions of different intraarticular tissues to the acute phase elevation of synovial fluid MMP-2 following rat ACL rupture. J Orthop Res. 27:243–248. 2009.PubMed/NCBI View Article : Google Scholar

21 

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.PubMed/NCBI View Article : Google Scholar

22 

Antony J and Huang RY: AXL-Driven EMT state as a targetable conduit in cancer. Cancer Res. 77:3725–3732. 2017.PubMed/NCBI View Article : Google Scholar

23 

Zhang G, Wang M, Zhao H and Cui W: Function of Axl receptor tyrosine kinase in non-small cell lung cancer. Oncol Lett. 15:2726–2734. 2018.PubMed/NCBI View Article : Google Scholar

24 

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.PubMed/NCBI View Article : Google Scholar

25 

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.PubMed/NCBI View Article : Google Scholar

26 

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.PubMed/NCBI View Article : Google Scholar

27 

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.PubMed/NCBI View Article : Google Scholar

28 

Wu G, Ma Z, Hu W, Wang D, Gong B, Fan C, Jiang S, Li T, Gao J and Yang Y: Molecular insights of Gas6/TAM in cancer development and therapy. Cell Death Dis. 8(e2700)2017.PubMed/NCBI View Article : Google Scholar

29 

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.PubMed/NCBI View Article : Google Scholar

30 

Zhang G, Wang M, Zhao H and Cui W: Function of Axl receptor tyrosine kinase in non-small cell lung cancer. Oncol Lett. 15:2726–2734. 2018.PubMed/NCBI View Article : Google Scholar

31 

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.PubMed/NCBI View Article : Google Scholar

32 

Scaltriti M, Elkabets M and Baselga J: Molecular pathways: AXL, a membrane receptor mediator of resistance to therapy. Clin Cancer Res. 22:1313–1317. 2016.PubMed/NCBI View Article : Google Scholar

33 

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

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Copy and paste a formatted citation
Spandidos Publications style
Han S, Wang Y, Ge C, Gao M, Wang X, Wang F, Sun L, Li S, Dong T, Dang Z, Dang Z, et al: Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma. Exp Ther Med 20: 41, 2020.
APA
Han, S., Wang, Y., Ge, C., Gao, M., Wang, X., Wang, F. ... Liu, N. (2020). Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma. Experimental and Therapeutic Medicine, 20, 41. https://doi.org/10.3892/etm.2020.9169
MLA
Han, S., Wang, Y., Ge, C., Gao, M., Wang, X., Wang, F., Sun, L., Li, S., Dong, T., Dang, Z., Cui, W., Zhang, G., Liu, N."Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma". Experimental and Therapeutic Medicine 20.5 (2020): 41.
Chicago
Han, S., Wang, Y., Ge, C., Gao, M., Wang, X., Wang, F., Sun, L., Li, S., Dong, T., Dang, Z., Cui, W., Zhang, G., Liu, N."Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma". Experimental and Therapeutic Medicine 20, no. 5 (2020): 41. https://doi.org/10.3892/etm.2020.9169
Copy and paste a formatted citation
x
Spandidos Publications style
Han S, Wang Y, Ge C, Gao M, Wang X, Wang F, Sun L, Li S, Dong T, Dang Z, Dang Z, et al: Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma. Exp Ther Med 20: 41, 2020.
APA
Han, S., Wang, Y., Ge, C., Gao, M., Wang, X., Wang, F. ... Liu, N. (2020). Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma. Experimental and Therapeutic Medicine, 20, 41. https://doi.org/10.3892/etm.2020.9169
MLA
Han, S., Wang, Y., Ge, C., Gao, M., Wang, X., Wang, F., Sun, L., Li, S., Dong, T., Dang, Z., Cui, W., Zhang, G., Liu, N."Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma". Experimental and Therapeutic Medicine 20.5 (2020): 41.
Chicago
Han, S., Wang, Y., Ge, C., Gao, M., Wang, X., Wang, F., Sun, L., Li, S., Dong, T., Dang, Z., Cui, W., Zhang, G., Liu, N."Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma". Experimental and Therapeutic Medicine 20, no. 5 (2020): 41. https://doi.org/10.3892/etm.2020.9169
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