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July-2014 Volume 32 Issue 1

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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.

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

Oncology Reports

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

Experimental and Therapeutic Medicine

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

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Oncology Letters

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

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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

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

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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

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Article

Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells

  • Authors:
    • Ling Xu
    • Xiujuan Qu
    • Heming Li
    • Ce Li
    • Jing Liu
    • Huachuan Zheng
    • Yunpeng Liu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, The First Hospital of China Medical University, Heping, Shenyang 110001, P.R. China, Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China
  • Pages: 318-324
    |
    Published online on: May 15, 2014
       https://doi.org/10.3892/or.2014.3183
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Abstract

Gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and we recently showed that lipid raft-regulated epidermal growth factor receptor (EGFR) activation antagonized TRAIL-induced apoptosis. However, it is not clear whether caveolin-1, an essential structural constituent of lipid rafts, regulates lipid raft-mediated EGFR activation. We report here that TRAIL induced the translocation of EGFR into lipid rafts and its activation in gastric cancer SGC-7901 and MGC-803 cells. Simultaneously, caveolin-1 was also activated. Knockdown of caveolin-1 partially prevented EGFR activation and increased TRAIL sensitivity. Moreover, TRAIL promoted the translocation of Src into lipid rafts and its activation, as well as the interaction of Src with both EGFR and caveolin-1. A Src inhibitor prevented these interactions and the activation of caveolin-1 and EGFR, and thus enhanced TRAIL-induced apoptosis. These data suggest that Src activates EGFR through the interaction of both Src-EGFR and Src-caveolin-1, and then antagonizes TRAIL-induced apoptosis in gastric cancer cells.
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1 

Cervantes A, Roda D, Tarazona N, Roselló S and Pérez-Fidalgo JA: Current questions for the treatment of advanced gastric cancer. Cancer Treat Rev. 39:60–67. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Schaefer U, Voloshanenko O, Willen D and Walczak H: TRAIL: a multifunctional cytokine. Front Biosci. 12:3813–3824. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Morizot A, Mérino D, Lalaoui N, et al: Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level. Cell Death Differ. 18:700–711. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Xu L, Qu X, Luo Y, et al: Epirubicin enhances TRAIL-induced apoptosis in gastric cancer cells by promoting death receptor clustering in lipid rafts. Mol Med Rep. 4:407–411. 2011.

5 

Cho IR, Koh SS, Min HJ, et al: Reovirus infection induces apoptosis of TRAIL-resistant gastric cancer cells by down-regulation of Akt activation. Int J Oncol. 36:1023–1030. 2010.PubMed/NCBI

6 

Van Schaeybroeck S, Kelly DM, Kyula J, Stokesberry S, Fennell DA, Johnston PG and Longley DB: Src and ADAM-17-mediated shedding of transforming growth factor-α is a mechanism of acute resistance to TRAIL. Cancer Res. 68:8312–8321. 2008.PubMed/NCBI

7 

Xu L, Zhang Y, Liu J, et al: TRAIL-activated EGFR by Cbl-b-regulated EGFR redistribution in lipid rafts antagonises TRAIL-induced apoptosis in gastric cancer cells. Eur J Cancer. 48:3288–3299. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Wang S, Yu S, Shi W, Ge L, Yu X, Fan J and Zhang J: Curcumin inhibits the migration and invasion of mouse hepatoma Hca-F cells through down-regulating caveolin-1 expression and epidermal growth factor receptor signaling. IUBMB Life. 63:775–782. 2011.

9 

Zhang B, Peng F, Wu D, Ingram AJ, Gao B and Krepinsky JC: Caveolin-1 phosphorylation is required for stretch-induced EGFR and Akt activation in mesangial cells. Cell Signal. 19:1690–1700. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Zhang J, Kalyankrishna S, Wislez M, et al: SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Am J Pathol. 170:366–376. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Wu T, Zhang B, Ye F and Xiao Z: A potential role for caveolin-1 in VEGF-induced fibronectin upregulation in mesangial cells: involvement of VEGFR2 and Src. Am J Physiol Renal Physiol. 304:F820–F830. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Chen Z, Bakhshi FR, Shajahan AN, et al: Nitric oxide-dependent Src activation and resultant caveolin-1 phosphorylation promote eNOS/caveolin-1 binding and eNOS inhibition. Mol Biol Cell. 23:1388–1398. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Wang Y, Roche O, Xu C, et al: Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible factor-mediated upregulation of caveolin-1. Proc Natl Acad Sci USA. 109:4892–4897. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Xu L, Qu X, Zhang Y, et al: Oxaliplatin enhances TRAIL-induced apoptosis in gastric cancer cells by CBL-regulated death receptor redistribution in lipid rafts. FEBS Lett. 583:943–948. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Irwin ME, Mueller KL, Bohin N, Ge Y and Boerner JL: Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. J Cell Physiol. 226:2316–2328. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Dittmann K, Mayer C, Kehlbach R and Rodemann HP: Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK. Mol Cancer. 7:692008. View Article : Google Scholar : PubMed/NCBI

17 

Sham D, Wesley UV, Hristova M and van der Vliet A: ATP-mediated transactivation of the epidermal growth factor receptor in airway epithelial cells involves DUOX1-dependent oxidation of Src and ADAM17. PLoS One. 8:e543912013. View Article : Google Scholar : PubMed/NCBI

18 

De Luca A, D’Alessio A, Gallo M, Maiello MR, Bode AM and Normanno N: Src and CXCR4 are involved in the invasiveness of breast cancer cells with acquired resistance to lapatinib. Cell Cycle. 13:148–156. 2014.PubMed/NCBI

19 

Samarakoon R, Chitnis SS, Higgins SP, Higgins CE, Krepinsky JC and Higgins PJ: Redox-induced Src kinase and caveolin-1 signaling in TGF-β1-initiated SMAD2/3 activation and PAI-1 expression. PLoS One. 6:e228962011.PubMed/NCBI

20 

Dittmann K, Mayer C, Kehlbach R, Rothmund MC and Peter Rodemann H: Radiation-induced lipid peroxidation activates src kinase and triggers nuclear EGFR transport. Radiother Oncol. 92:379–382. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Gottlieb-Abraham E, Shvartsman DE, Donaldson JC, Ehrlich M, Gutman O, Martin GS and Henis YI: Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites. Mol Biol Cell. 24:3881–3895. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Chen J, Chen JK and Harris RC: Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway. Mol Cell Biol. 32:981–991. 2012. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Xu L, Qu X, Li H, Li C, Liu J, Zheng H and Liu Y: Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells. Oncol Rep 32: 318-324, 2014.
APA
Xu, L., Qu, X., Li, H., Li, C., Liu, J., Zheng, H., & Liu, Y. (2014). Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells. Oncology Reports, 32, 318-324. https://doi.org/10.3892/or.2014.3183
MLA
Xu, L., Qu, X., Li, H., Li, C., Liu, J., Zheng, H., Liu, Y."Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells". Oncology Reports 32.1 (2014): 318-324.
Chicago
Xu, L., Qu, X., Li, H., Li, C., Liu, J., Zheng, H., Liu, Y."Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells". Oncology Reports 32, no. 1 (2014): 318-324. https://doi.org/10.3892/or.2014.3183
Copy and paste a formatted citation
x
Spandidos Publications style
Xu L, Qu X, Li H, Li C, Liu J, Zheng H and Liu Y: Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells. Oncol Rep 32: 318-324, 2014.
APA
Xu, L., Qu, X., Li, H., Li, C., Liu, J., Zheng, H., & Liu, Y. (2014). Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells. Oncology Reports, 32, 318-324. https://doi.org/10.3892/or.2014.3183
MLA
Xu, L., Qu, X., Li, H., Li, C., Liu, J., Zheng, H., Liu, Y."Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells". Oncology Reports 32.1 (2014): 318-324.
Chicago
Xu, L., Qu, X., Li, H., Li, C., Liu, J., Zheng, H., Liu, Y."Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells". Oncology Reports 32, no. 1 (2014): 318-324. https://doi.org/10.3892/or.2014.3183
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