Journal of Chest Surgery

  • 제50권3호
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  • Pages.153-162
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  • 2017
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  • 2765-1606(pISSN)
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  • 2765-1614(eISSN)
대한심장혈관흉부외과학회 (The Korean Society for Thoracic and Cardiovascular Surgery)
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The Antitumor Effect of C-terminus of Hsp70-Interacting Protein via Degradation of c-Met in Small Cell Lung Cancer

  • Cho, Sung Ho (Department of Thoracic and Cardiovascular Surgery, Kosin University Gospel Hospital, Kosin University College of Medicine) ;
  • Kim, Jong In (Department of Thoracic and Cardiovascular Surgery, Kosin University Gospel Hospital, Kosin University College of Medicine) ;
  • Kim, Hyun Su (Department of Thoracic and Cardiovascular Surgery, Kosin University Gospel Hospital, Kosin University College of Medicine) ;
  • Park, Sung Dal (Department of Thoracic and Cardiovascular Surgery, Kosin University Gospel Hospital, Kosin University College of Medicine) ;
  • Jang, Kang Won (Yonsei Research Institute of Aging Science, Yonsei University)
  • 투고 : 2016.08.05
  • 심사 : 2016.10.17
  • 발행 : 2017.06.05
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초록

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.

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피인용 문헌

  1. MET Inhibitors in Small Cell Lung Cancer: From the Bench to the Bedside vol.11, pp.10, 2017, https://doi.org/10.3390/cancers11101404
  2. With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage vol.10, pp.11, 2017, https://doi.org/10.3390/cells10113121