NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway

Changming Liu1, Mingxiong Sheng1, Liheng Lin1

  • 1The Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian 355000, People's Republic of China.

Abstract

Insights

Nanog homeobox (NANOG) regulates prostate cancer stem cell (PCSC) growth by influencing the TGF-β1/SMAD pathway. This suggests NANOG is a potential therapeutic target for overcoming castration resistance in prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Castration resistance in prostate cancer often leads to mortality.
  • Prostate cancer stem cells (PCSCs) are implicated in the development of castration resistance.
  • The roles of NANOG and TGF-β1/SMAD signaling in PCSCs are not fully understood.

Purpose of the Study:

  • To investigate the effect of NANOG on PCSC proliferation.
  • To determine the involvement of the TGF-β1/SMAD signaling pathway in NANOG-mediated PCSC regulation.

Main Methods:

  • Isolation of CD44+/CD133+/NANOG+ PCSCs from DU145 cells using flow cytometry.
  • Silencing of NANOG using short hairpin RNA (shRNA).
  • Assessment of PCSC biological behavior and TGF-β1/SMAD signaling pathway activity.

Main Results:

  • NANOG expression suppressed PCSC proliferation and induced apoptosis.
  • NANOG inhibited cell cycle progression at the G0/G1 phase.
  • Reduction in TGF-β1, p15, and p-SMAD2 expression was observed following NANOG silencing.

Conclusions:

  • NANOG positively regulates PCSC growth via the TGF-β1/SMAD signaling pathway.
  • NANOG plays a critical role in maintaining PCSC characteristics relevant to castration resistance.

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