Role of ZEB Family Members in Proliferation, Metastasis, and Chemoresistance of Prostate Cancer Cells: Revealing Signaling Networks

Abstract

Prostate cancer (PCa) is one of the leading causes of death worldwide. A variety of strategies, including surgery, chemotherapy, radiotherapy, and immunotherapy, are applied for PCa treatment. PCa cells are responsive towards therapy at early stages, but they can obtain resistance in the advanced stage. Furthermore, their migratory ability is high in advanced stages. It seems that genetic and epigenetic factors play an important role in this case. Zinc finger E-box-binding homeobox (ZEB) is a family of transcription with two key members, including ZEB1 and ZEB2. ZEB family members are known due to their involvement in promoting cancer metastasis via EMT induction. Recent studies have shown their role in cancer proliferation and inducing therapy resistance. In the current review, we focus on revealing the role of ZEB1 and ZEB2 in PCa. ZEB family members are able to significantly promote the proliferation and viability of cancer cells. ZEB1 and ZEB2 enhance migration and invasion of PCa cells via EMT induction. Overexpression of ZEB1 and ZEB2 is associated with a poor prognosis of PCa. ZEB1 and ZEB2 upregulation occurs during PCa progression and can provide therapy resistance to cancer cells. PRMT1, Smad2, and non-coding RNAs can function as upstream mediators of the ZEB family. Besides, Bax, Bcl-2, MRP1, Ncadherin, and E-cadherin can be considered as downstream targets of the ZEB family in PCa.

Keywords: Prostate cancer; chemoresistance; epithelialto- mesenchymal transition (EMT); lncRNA.; metastasis; microRNA; proliferation; zinc finger E-box-binding homeobox (ZEB).