Effect of transglutaminase 2 on survival and invasion of lung cancer cells

• Main Authors: Wuan-Chun, 陳宛君
• Other Authors: 李宜儒
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/39489979740939533083

碩士 === 中山醫學大學 === 微生物免疫研究所 === 100 === Lung cancer is the leading cause of cancer death worldwide. Given that the major threat of cancer to life is distant metastasis, we aimed to delineate the molecular mechanism underlying lung cancer metastasis. Transglutaminase 2 (TG2), belonging to the transglutaminase superfamily, is ubiquitously expressed. It localizes mainly in the cytosol, but also appears in the nucleus, plasma membrane, cell surface and extracellular space. TG2 possesses multiple enzymatic activities, including the most well-known transglutaminase as well as GTPase, protein kinase and protein disulphide isomerase activities. Nevertheless, it can associate with integrin on the cell surface, thereby facilitating cell adhesion to fibronectin. Recent findings further reveal its involvement in drug resistance and tumor metastasis of breast cancer cells. Here we explore the role of TG2 in metastasis of lung cancer cells. Our results show that the highly invasive lung cancer cell line CL1-5 display higher levels of TG2 than its parental line CL1-0, which shows low extent of invasion. CL1-5 is also more resistant to anoikis, a type of apoptosis induced by cell detachment, and the treatment of doxorubicin, a drug used in chemotherapy. Overexpression of TG2 in CL1-0 enhances cell migration and invasion, but exerts no effect on the anoikis resistance and drug resistance. Cells with higher TG2 expression also have greater levels of external TG2. Application of recombinant TG2 into CL1-0 substantially enhances the extents of migration and invasion. Thus, TG2 plays a positive role in cell migration and invasion, and this might confer the metastatic capacity of lung cancer cells.