MTA family of proteins in prostate cancer: biology, significance, and therapeutic opportunities

This review summarizes our current understanding of the role of MTA family members, particularly MTA1, with a special emphasis on prostate cancer. The interest for the role of MTA1 in prostate cancer was boosted from our initial findings of MTA1 as a component of "vicious cycle" and a member of bone metastatic signature. Analysis of human prostate tissues, xenograft and transgenic mouse models of prostate cancer, and prostate cancer cell lines has provided support for the role of MTA1 in advanced disease and its potential role in initial stages of prostate tumor progression. Recent discoveries have highlighted a critical role for MTA1 in inflammation-triggered prostate tumorigenesis, epithelial-to-mesenchymal transition, prostate cancer survival pathways, and site metastasis. Evidence for MTA1 as an upstream negative regulator of tumor suppressor genes such as p53 and PTEN has also emerged. MTA1 is involved in prostate tumor angiogenesis by regulating several pro-angiogenic factors. Evidence for MTA1 as a prognostic marker for aggressive prostate cancer and disease recurrence has been described. Importantly, pharmacological dietary agents, namely resveratrol and its analogs, are potentially applicable to prostate cancer prevention, treatment, and control of cancer progression due to their potent inhibitory effects on MTA proteins.