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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.5
- 수록면
- 363 - 370 (8page)
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Extrahepatic cholangiocarcinoma (ECC), a malignant tumor of biliary origin, has a poor prognosis with limited treatment options. The KRAS oncogene is the most commonly mutated gene in ECC and one of the factors that predicts a poor prognosis and low survival rate. L1 cell adhesion molecule (L1CAM) is expressed in ECC cells and acts as an independent poor prognostic factor in predicting patient survival. In this study we investigate the functional significance of L1CAM in ECC cells with activating KRAS mutation. We selected an ECC cell line, EGI-1, with activating KRAS mutation, and then confirmed its expression of L1CAM by RT-PCR, western blot analysis, and flow cytometry. The suppression of L1CAM expres-sion (using a specific lentivirus-delivered shRNA) significantly decreased the migratory and invasive properties of EGI-1 cells, without altering their proliferation or survival. Analyses of signaling effectors in L1CAM-depleted and control EGI-1 cells indicated that L1CAM suppression decreased the levels of both phosphorylated MKK4 and total MKK4, together with c-Jun N-terminal kinase (JNK) phosphorylation. Further, exposure to a JNK inhibitor (SP600125) decreased migration and invasion of EGI-1 cells. These results suggest that L1CAM promotes cellular migration and invasion via the induction of MKK4 expression, leading to JNK activation. Our study is the first to demonstrate a functional role for L1CAM in ECC carrying the activating KRAS mutation. Given that KRAS is the most commonly mutated oncogene in ECC, L1CAM may serve as an attractive therapeutic target for ECC cells with activating KRAS mutation.
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참고문헌 (56)
참고문헌 신청
Altevogt, P. / 2016 / L1CAM in human cancer / Int. J. Cancer 138:1565~1576
Arlt, M. J. / 2006 / Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment / Cancer Res 66:936~943
Bengala, C. / 2010 / Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial / Br. J. Cancer 102:68~72
Blechacz, B. / 2008 / Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment / Hepatology 48:308~321
Blechacz, B. / 2011 / Clinical diagnosis and staging of cholangiocarcinoma / Nat. Rev. Gastroenterol. Hepatol 8:512~522
Arlt, M. J. / 2006 / Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment / Cancer Res 66:936~943
Bengala, C. / 2010 / Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial / Br. J. Cancer 102:68~72
Blechacz, B. / 2008 / Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment / Hepatology 48:308~321
Blechacz, B. / 2011 / Clinical diagnosis and staging of cholangiocarcinoma / Nat. Rev. Gastroenterol. Hepatol 8:512~522
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