title: Androgen receptor enhances entosis, a non-apoptotic cell death, through modulation of Rho/ROCK pathway in prostate cancer cells.
abstract: BACKGROUND
  Cell-in-cell phenomenon has been found for more than a century. Entosis, which is a newly found homogeneous cell-in-cell phenomenon and a non-apoptosis cell death progress, has unclear function in prostate cancer progression. Here, we dissected mechanism of AR signaling related to entosis incidence in PCa progression.
  
  
  METHODS
  Two stable PCa cell lines, named LNCaP-ARsi and C4-2-ARsi were established with stably transfected AR-shRNA to knockdown AR mRNA expression in LNCaP and C4-2 cells, respectively. PC3-AR9 cell line was also established after stably transfecting full-length AR-cDNA into PC3 cells. All these cells were cultured in poly-HEME-coated plates to induce entosis, which is demonstrated via double staining.
  
  
  RESULTS
  Androgen-DHT could enhance entosis in LNCaP, C4-2 and PC3-AR9 PCa cells in a dose dependent manner. Knock-down of AR in LNCaP and C4-2 significantly suppressed entosis as compared to LNCaP-ARsc and C4-2-ARsc cells at both 1 and 10 nM DHT condition (P < 0.05). And suppression of Rho/ROCK expression resulted in interruption of AR-mediated entosis. Human PCa samples surveys demonstrated that entosis was found only in CRPC but not in BPH and ADPC where AR was less expressed as compared to CRPC.
  
  
  CONCLUSIONS
  These results indicated that AR might play a negative role during PCa progression via influencing entosis by modulating Rho/ROCK pathway. This newly identified AR role of enhancing entosis might help us to better understand the multiple and opposite roles of AR, which could either promote or suppress PCa cell progression via different mechanisms.
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China.
authors.forename: Simeng
authors.initials: S
authors.lastname: Wen
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Shang
authors.forename: Shimiao
authors.initials: S
authors.lastname: Zhu
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Niu
mesh_terms: D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D057691:Entosis / Q000502:physiology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D011944:Receptors, Androgen / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D054460:rho-Associated Kinases / Q000502:physiology*
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D054460:rho-Associated Kinases
keywords: Rho/ROCK pathway; androgen receptor; entosis