Plk1-dependent microtubule dynamics promotes androgen receptor signaling in prostate cancer

Xianzeng Hou, Zhiguo Li, Weize Huang, Jiejie Li, Christopher Staiger, Shihuan Kuang, Tim Ratliff, Xiaoqi Liu

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


BACKGROUND The androgen receptor (AR) signaling continues to be essential in castrate-resistant prostate cancer (CRPC). Taxel-based chemotherapy is the current standard treatment for CRPC patients. Unfortunately, almost all patients eventually develop resistance toward this chemotherapy. Significantly, it was recently found that the anti-tumor effect of paclitaxel in CRPC is due to its inhibition of AR activity via its inhibition of microtubule dynamics. Polo-like kinase 1 (Plk1), a critical regulator in many cell cycle events, is elevated in prostate cancer (PCa) and linked to tumor grades. Of note, we have previously shown that Plk1 phosphorylates CLIP-170 and p150Glued, two important regulators of microtubule dynamics. METHODS We compared paclitaxel-mediated phenotypes (inhibition of the AR signaling, decrease of microtubule dynamics and cell death) of PCa cells expressing different forms of CLIP-170 and p150 Glued with different Plk1 phosphorylation states. RESULTS We show that Plk1 phosphorylation of CLIP-170 and p150Glued affects cellular responses to paclitaxel. Expression of Plk1-unphosphorylatable mutants of CLIP-170 and p150Glued results in increased paclitaxel-induced apoptosis, increased protein degradation of the AR, and decreased nuclear accumulation of the AR in response to androgen in prostate cancer cells. Finally, we show that cells expressing unphosphorylatable mutants of CLIP-170 have defective microtubule dynamics, thus providing a new mechanism to understand how Plk1-associated kinase activity promotes constitutive activation of AR signaling in CRPC. CONCLUSIONS Our data suggest that a combination of inhibition of Plk1 and paclitaxel might be a novel avenue for treatment of CRPC.

Original languageEnglish
Pages (from-to)1352-1363
Number of pages12
Issue number12
StatePublished - Sep 2013


  • Plk1
  • androgen receptor
  • microtubule dynamics
  • paclitaxel
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology


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