Studies of the Matrix Molecule CCN1 Modulating TGF1-Induced Activities in Lung Carcinomas

• Main Authors: Chu-Jen Lin, 林祝任
• Other Authors: Shr-Jeng Leu
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/09535128431854332422

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 101 === The CCN1 protein, a member of the matricellular CCN family, is a secreted cysteine-rich matrix molecule. CCN1 regulates multiple cellular actions. Abnormal expression of CCN1 is highly associated with a variety of human diseases including multiple cancers. Studies showed that CCN1 may play a suppressing role in human non-small cell lung carcinomas (NSCLCs) that expression of CCN1 is inversely correlated with malignancy of NSCLCs and high expression levels of CCN1 associate with enhancement of patient survival. The molecular mechanism underlying CCN1-induced lung cancer suppression remains to be explored. The TGF1 is capable of inducing epithelial-mesenchymal transition (EMT) to accelerate tumor metastasis. CCN family is composed of four conserved structural domains. In the present study, we focus on structure-function relationship of the CCN1 and aim to define the structural region of CCN1 for anti-cancer activities. We generated various CCN1 structural mutants as well as the deletion mutants that were overexpressed in lung cancer cells by the lentivirus expression strategy. Our results showed that TGF-induced EMT process and cellular migration were attenuated by the presence of CCN1 overexpression, while these effect were not observed in the cells that overexpressed CCN1 variants with defective mutations in the fourth domain. Thus, the intrinsic activity of CCN1 in suppressing NSCLC can be defined in the domain IV fragment of CCN1, the CCN1-D4. Furthermore, by in vivo angiogenesis assay, unlike the full-length CCN1, the CCN1-D4 protein was not capable of inducing angiogenesis. Taken together, the data suggest that CCN1-D4 protein fragment may be the developed as a basis of designing an effective reagent targeting NSCLCs.