You are here

| Adult Stem Cells

Describing the Role of Sox2 in the Murine Adult Prostate

Review of “Sox2 Expression Marks Castration‐Resistant Progenitor Cells in the Adult Murine Prostate” from STEM CELLS by Stuart P. Atkinson 

The pluripotency-associated SOX2 (sex determining region Y‐box 2) transcription factor has recently been reported to promote lineage plasticity and anti-androgen resistance in prostate cancer [1] and several studies, including one from the laboratory of Donald J. Vander Griend (The University of Illinois at Chicago, Chicago, Illinois, USA), have established that a subpopulation of ΔNp63‐positive human basal prostate epithelial cells also express SOX2 [2, 3]. 

To fully delineate the role of this transcription factor in the healthy prostate, researchers from the Vander Griend laboratory now return with a STEM CELLS study that examines whether Sox2 marks a progenitor compartment competent for prostate homeostasis and regeneration in vivo [4]. Interestingly, McAuley et al. now describe how lineage tracing experiments in a mouse model led them to postulate that Sox2+ cells are castration‐resistant and contribute to the regeneration of the prostate.

Overall, the authors established that epithelial cells of the proximal prostate adjacent to the urethra display an enrichment for Sox2 expression when compared to distal regions, and via lineage tracing (via a Sox2CreER driver) during prostatic development, homeostasis, and regeneration, they also report that the Sox2-positive lineage self-renews and contributes to androgen‐mediated regeneration of the prostate. Interestingly, their analyses also uncovered the persistence of Sox2-expressing luminal cells after castration, suggesting the role of Sox2 in both castration-resistance and cell survival, as well as prostatic regeneration.

This new research describes a new prostate progenitor cell population and implicates Sox2 as a critical regulatory factor in adult prostate epithelial stem cells and has prompted other interesting ongoing lines of research. These include the question of the preprogrammed or acquired cellular resistance to hormone‐targeted therapies and whether targeting these mechanisms can increase therapeutic efficacy in prostate disease. Furthermore, studies will also aim to understand Sox2 expression in prostate tumor cells via the investigation of SOX2‐expressing lineages within the normal and malignant human prostate epithelium.

For more on Sox2 and progenitors/stem cells in the prostate, stay tuned to the Stem Cells Portal!

References

  1. Mu P, Zhang Z, Benelli M, et al., SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 2017;355:84-88.
  2. Kregel S, Kiriluk KJ, Rosen AM, et al., Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer. PLoS One 2013;8:e53701.
  3. Yu X, Cates JM, Morrissey C, et al., SOX2 expression in the developing, adult, as well as, diseased prostate. Prostate Cancer and Prostatic Disease 2014;17:301-9.
  4. McAuley E, Moline D, VanOpstall C, et al., Sox2 Expression Marks Castration-Resistant Progenitor Cells in the Adult Murine Prostate. STEM CELLS 2019;37:690-700.