Abstract
Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.
Highlights
Transforming growth factor-beta (TGF-β) emerges as one of the key regulators of tumor development and progression
testicular germ cell tumors (TGCTs) develop from cells of germ cell neoplasia in situ (GCNIS), which originate from gonocytes that fail to undergo physiological spermatogenic differentiation [35]
The role of transforming factor β (TGF-β) in prostate tumors is a broad topic that has been extensively earlier reviewed [227,228,229,230], here we only provide a short outline of the mechanism of TGF-β actions in prostatic cancer cells
Summary
Transforming growth factor-beta (TGF-β) emerges as one of the key regulators of tumor development and progression. At the beginning of tumor development, TGF-β attenuates cancerous proliferation, limiting tumor growth During cancer progression, these tumor suppressive effects reverse, and TGF-β starts to promote migration, invasion, and formation of distant metastasis [1]. TGF-β actions could result from interplay with the activity of microRNAs, which emerge as important modulators and mediators of TGF-β effects in cancer cells. These small, non-coding RNAs are involved in the control of a wide array of critical biological processes, including cells development, proliferation, growth, differentiation, and apoptosis. Genitourinary cancers (GCs) represent 25% of all solid tumors [4] They derive from different types of cells located in the kidney, penis, testis, bladder, and prostate [5,6]. Surgery plays a fundamental role in the radical treatment of all genitourinary cancers, it can be complemented by local or systemic chemotherapy, radiation therapy, local or systemic immunotherapy, hormonal therapy, or targeted therapies
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