Pre-clinical investigation of STAT3 pathway in bladder cancer: Paving the way for clinical translation
Sepideh Mirzaei, Mohammad Gholami, Mahmood Khaksary Mahabady, Noushin Nabavi, Amirhossein Zabolian, Seyed Mohammad Banihashemi, Amirabbas Haddadi, Maliheh Entezari, Kiavash Hushmandi, Pooyan Makvandi, Saeed Samarghandian, Ali Zarrabi, Milad Ashrafizadeh, Haroon Khan
Abstract
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.