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.
Subject(s)
MicroRNAs , Prostatic Neoplasms , Cell Line, Tumor , Cell Movement , Cell Proliferation , Drug Resistance, Neoplasm , Epithelial-Mesenchymal Transition , Homeodomain Proteins/genetics , Humans , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Protein-Arginine N-Methyltransferases , Repressor Proteins , Zinc Finger E-box Binding Homeobox 2/genetics , Zinc Finger E-box-Binding Homeobox 1/geneticsABSTRACT
Effective cancer therapy requires identification of signaling networks and investigating their potential role in proliferation and invasion of cancer cells. Among molecular pathways, signal transducer and activator of transcription 3 (STAT3) has been of importance due to its involvement in promoting proliferation, and invasion of cancer cells, and mediating chemoresistance. In the present review, our aim is to reveal role of STAT3 pathway in bladder cancer (BC), as one of the leading causes of death worldwide. In respect to its tumor-promoting role, STAT3 is able to enhance the growth of BC cells via inhibiting apoptosis and cell cycle arrest. STAT3 also contributes to metastasis of BC cells via upregulating of MMP-2 and MMP-9 as well as genes in the EMT pathway. BC cells obtain chemoresistance via STAT3 overexpression and its inhibition paves the way for increasing efficacy of chemotherapy. Different molecular pathways such as KMT1A, EZH2, DAB2IP and non-coding RNAs including microRNAs and long non-coding RNAs can function as upstream mediators of STAT3 that are discussed in this review article.