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Androgen receptor plays critical role in regulating cervical cancer cell migration

Sarpita Bose1, Subhrangshu Das1, Sebabrata Maity2

  • 1Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, IICB TRUE Campus, CN-6, Sector 5, Salt Lake, Kolkata, 700091, WB, India.

Molecular and Cellular Endocrinology
|May 23, 2025
PubMed

Insights

Androgen receptor (AR) is significantly downregulated in cervical cancer (CC). Restoring AR levels can reverse cancer cell invasiveness by impacting cell migration and cytoskeletal dynamics, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Cervical cancer (CC) is a significant global health issue, particularly in India.
  • Existing research on CC genetics and pathways needs expansion for novel therapeutic targets in metastatic disease.

Purpose of the Study:

  • To identify novel interacting proteins crucial for cervical cancer progression using network analysis.
  • To investigate the role of the Androgen receptor (AR) as a potential therapeutic target in cervical cancer.

Main Methods:

  • Graph-theory-based network analysis to identify important interacting proteins (IIPs).
  • Analysis of patient samples, ex vivo, and in vitro experiments to assess AR expression and function.
  • Investigating AR's downstream signaling pathways (PTEN, PI3K/AKT) and effects on cell migration and cytoskeletal dynamics.

Main Results:

  • Androgen receptor (AR) identified as a key, understudied regulator in cervical cancer with significant downregulation.
  • Exogenous AR expression reduced cancer cell migration and reversed epithelial-to-mesenchymal transition (EMT) markers.
  • AR signaling modulated the PTEN/PI3K/AKT pathway, impacting GSK3β activity and mesenchymal marker degradation.
  • AR disrupted cytoskeletal dynamics by altering the RhoA/ROCK1/LIMK1/CFL1 pathway, reducing cell motility and spread.

Conclusions:

  • Androgen receptor (AR) plays a critical role in regulating cervical cancer cell invasiveness and motility.
  • Restoring AR function presents a promising therapeutic strategy for combating cervical cancer metastasis.
  • Targeting AR signaling pathways could offer a novel approach for cervical cancer treatment.
Keywords:
Androgen receptorCervical cancerEMTPPINPTENRhoA

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