Functional characterization and mechanistic investigation of the calcium-activated neutral protease 8 (CAPN8) in lung cancer progression.

• Main Authors: Chia-Yu Chang, 張家瑜
• Other Authors: CHIEN-WEI CHEN
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107NCHU5114005%22.&searchmode=basic

碩士 === 國立中興大學 === 生物醫學研究所 === 107 === Lung cancer is the top of ten malignant tumors in Taiwan. The high mortality rate of lung cancer is related to the difficulty in early detection and in effective treatment in the advanced stage. In most patients, the epidermal growth factor receptor (EGFR) was inappropriately activated and associated with poor prognosis. Gefitinib, a tyrosine kinase inhibitor (TKI) of EGFR, has been the first line treatment for lung adenocarcinoma patients with activated EGFR mutations. However, such drugs have therapeutic limitations for the primary and acquired drug resistance in the lung cancer treatment. In previous studies, the performance of the CAPN8 gene is different between the cell lines sensitive and resistant to Gefitinib, which may affect one of the reasons for the lung cancer cells sensitive to Gefitinib. CAPN8 is a member of the family of mammalian calpain proteases, which are Calcium-sensitive cysteine-proteases, main function is to regulate intracellular calcium. However, the role and function of CAPN8 in lung cancer is unclear. In order to understand the effect of CAPN8 in lung cancer, CAPN8 was transfected into CL1-5 and H1299 cell lines which have lower endogenous CAPN8 expression and set up the stable cell lines. Overexpression of CAPN8 in CL1-5 would enhance cancer cell migration, invasion, and colony formation function, but on the contrary, it could be inhibited capability of migration, invasion, and colony formation in H1299. Moreover, CAPN8 overexpression in H1299 cell line could significantly suppress turmor growth in vivo compared with the control group. In addition, nuclear membrane protein separation and immunofluorescence staining experiments showed that CAPN8 is mainly expressed in the cytoplasm. Furthermore, we found that overexpression of CAPN8 could increase the cells resistance to Gefitinib in both cells and affect the pathway of EGFR and Src, to regulate cancer cell function. Taken together, the results revealed that CAPN8 may regulate migration, invasion and drug resistance of lung cancer cells through the EGFR and Src pathways. These findings will provide a new direction to develop the treatment strategy for lung cancer.