Androgen receptor expression reduces stemness characteristics of prostate cancer cells (PC3) by repression of CD44 and SOX2
JournalJournal of Cellular Biochemistry
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AbstractStudies have shown that a subgroup of tumor cells possess stemness characteristics having self-renewal capacity and the ability to form new tumors. We sought to identify the plausible stemness factor that determines the "molecular signature" of prostate cancer (PCa) cells derived from different metastases (PC3, PCa2b, LNCaP, and DU145) and whether androgen receptor (AR) influences the maintenance of stemness features. Here we show sex-determining region Y (SRY)-box 2 (SOX2) as a putative stem cell marker in PC3 PCa cells and not in DU145, PCa2b, or LNCaP cells. PCa2b and PC3 cells were derived from bone metastases. PCa2b cells which are positive for the AR failed to demonstrate the expression of either cluster of differentiation 44 (CD44) or SOX2. Knockdown (KD) of AR in these cells did not affect the expression of either CD44 or SOX2. Conversely, PC3 cells, which are negative for AR, expressed both CD44 and SOX2. However, the expression of AR downregulated the expression of both CD44 and SOX2 in PC3 cells. CD44 regulates SOX2 expression as KD of CD44 and reduces SOX2 levels considerably. SOX2 KD attenuated not only the expression of SNAIL and SLUG but also the migration and tumorsphere formation in PC3 cells. Collectively, our findings underscore a novel role of CD44 signaling in the maintenance of stemness and progression of cancer through SOX2 in AR-independent PC3 cells. SOX2 has a role in the regulation of expression of SNAIL and SLUG. SOX2 could be a potential therapeutic target to thwart the progression of SOX2-positive cancer cells or recurrence of androgen-independent PCa. © 2018 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
SponsorsWe thank Dr C. K. Choo (University of Hong Kong, Hong Kong, China) for HPR1 cell line. We thank Dr Joseph Mauban at Confocal Microscopy Core (University of Maryland, Baltimore, MD) for providing technical assistance in using the Zeiss LSM 510 META Confocal Laser Scanning Microscope. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01 AR066044 to MAC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
cancer stem cells, cluster of differentiation 44
sex-determining region Y (SRY)-box 2
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85053383467&doi=10.1002%2fjcb.27573&partnerID=40&md5=ff404d3348a03eae571ae05053a04097; http://hdl.handle.net/10713/8580