Cancer Stem Cells and Androgen Receptor Signaling: Partners in Disease Progression

Abstract

Cancer stem cells exhibit self-renewal, tumorigenesis, and a high differentiation potential. These cells have been detected in every type of cancer, and different signaling pathways can regulate their maintenance and proliferation. Androgen receptor signaling plays a relevant role in the pathophysiology of prostate cancer, promoting cell growth and differentiation processes. However, in the case of prostate cancer stem cells, the androgen receptor negatively regulates their maintenance and self-renewal. On the other hand, there is evidence that androgen receptor activity positively regulates the generation of cancer stem cells in other types of neoplasia, such as breast cancer or glioblastoma. Thus, the androgen receptor role in cancer stem cells depends on the cellular context. We aimed to analyze androgen receptor signaling in the maintenance and self-renewal of different types of cancer stem cells and its action on the expression of transcription factors and surface markers associated with stemness.

Frequency of Androgen Receptor Positivity in Tumors: A Study Evaluating More Than 18,000 Tumors

“…Such activated AR binds to androgen response elements together with co-regulators and leads to the transcriptional regulation of a large variety of target genes. However, the number and kind of AR-co-regulators and AR-responsive genes in different normal and cancerous tissues, particularly in cancers other than prostatic tumors, and the impact of the level of AR are still the subjects of current research [50][51][52]. The theory that low-level AR expression is non-random is supported by the significantly higher rate of positive AR immunostaining in "non-genital" tumors from male than from female patients.…”

Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression

“…Tumor cells are in a dynamic state of mutation and clonal evolution, and the plasticity of PCSCs in response to targeted therapy leads to the generation of different subclonal tumor cells. The high tumorigenicity of PCSCs also generates a small population of drug-resistant cells that eventually become the dominant cell population in the tumor tissue, leading to treatment failure ( Mia et al, 2023 ; Quintero et al, 2023 ). Moreover, PCSCs engage in intricate interactions with cytokines, signaling molecules, the ECM, and other factors in the adjacent TME.…”