Formation of Secretory Senescent Cells in Prostate Tumors: The Role of Androgen Receptor Activity and Cell Cycle Regulation



Year of publication 2013
Type Chapter of a book
MU Faculty or unit

Faculty of Medicine

Description The induction of senescence in cancer cells is believed to be a potent mechanism of tumor suppression; however, senescent cells remain metabolically active and secrete a broad spectrum of factors, modulate the tissue microenvironment, and potentially promote tumorigenicity in neighboring malignant cells. Another important subpopulation of secretory cells modulating the prostate tissue microenvironment is represented by neuroendocrine cells. Interestingly, androgen deprivation therapy, a widely used treatment for advanced prostate cancer, induces both the emergence of neuroendocrine-like prostate cancer cells and the senescence-associated secretory phenotype in prostate cancer epithelial cells. The induction of the senescence-associated secretory phenotype by androgen depletion is tightly connected with the regulation of the cell cycle machinery through the downregulation of S-phase kinase-associated protein 2, whereas the emergence of neuroendocrine-like cancer cells (through the process of neuroendocrine differentiation) is under separate control. In this chapter, we summarize possible mechanisms and consequences of the formation of the aforementioned secretory phenotypes in prostate tumors and the role of the androgen receptor and cell cycle regulation in these processes.
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