The role of Clusterin in cancer metastasis

Mei Peng,1,2 Jun Deng,2 Sichun Zhou,2 Ting Tao,2 Qiongli Su,2 Xue Yang,1 Xiaoping Yang21Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, People’s Republic of ChinaAbstract: Clusterin is a conserved glycoprotein that has been characterized from almost all human tissues and fluids and plays a key role in cellular stress response and survival. Recently, research efforts have been contributed to explore the function of Clusterin in cancer metastasis, which is particularly important to design the strategies for treating metastatic patients. Evidence collected has demonstrated that Clusterin is overexpressed in tumor metastatic patients and experimental metastasis models. Specifically, Clusterin has been shown to have the role in anti-apoptotic capacities, development of therapy resistance and induction of epithelial–mesenchymal transition, all associated with cancer metastasis. Inhibition of Clusterin is known to increase the cytotoxic effects of chemotherapeutic agents and improves advanced cancer patients survival in clinical trials. Our unpublished data have demonstrated that Clusterin is overexpressed in bladder cancer and metformin, a well-known metabolism modulator specifically targets Clusterin by inhibiting migration of bladder cancer cells. In this review, we provide a general view of how Clusterin modulates cancer metastasis and update current understanding of detailed molecular mechanisms underlying of Clusterin for developing cancer management in future.Keywords: Clusterin, metastasis, EMT, apoptosis, drug resistanc