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CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations

Anchit Khanna1,2, Jayant K Rane3, Kati K Kivinummi1,4

  • 1Prostate Cancer Research Center (PCRC), Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere and Tampere University Hospital, Tampere, Finland.

Oncotarget
|May 13, 2015
PubMed

Insights

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is overexpressed in prostate cancer and its stem cells. Targeting CIP2A may offer a new therapeutic strategy for castration-resistant prostate cancer (CRPC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) presents clinical challenges due to residual androgen receptor (AR) signaling and cancer stem-like cells (SCs).
  • Identifying therapeutic targets common to both AR signaling and cancer SCs is a promising strategy for CRPC treatment.

Purpose of the Study:

  • To identify AR-target proteins overexpressed in prostate cancer stem cells.
  • To investigate the role of Cancerous inhibitor of protein phosphatase 2A (CIP2A) as a potential therapeutic target in CRPC.

Main Methods:

  • Analysis of over 300 clinical prostate cancer samples and patient-derived prostate epithelial cultures (PPECs).
  • Investigated AR binding to the CIP2A gene and its regulation of CIP2A expression at mRNA and protein levels.
  • Assessed the effect of CIP2A depletion on cell viability, colony formation, and anchorage-independent growth in prostate cancer cell models.

Main Results:

  • CIP2A was significantly overexpressed in both hormone-naïve prostate cancer (HN-PC) and CRPC patients, with 3-fold and 30-fold increases in HN-PC and CRPC SCs, respectively.
  • Demonstrated in vivo binding of AR to the CIP2A intronic region and showed that AR positively regulates CIP2A expression.
  • Depletion of CIP2A reduced cell viability and colony formation in both AR-independent and AR-responsive prostate cancer cells, impairing anchorage-independent growth.

Conclusions:

  • CIP2A is identified as a common factor linking AR signaling and cancer stem cell functionality in prostate cancer.
  • CIP2A represents a potential therapeutic target for castration-resistant prostate cancer, addressing a critical unmet need in prostate cancer treatment.
Keywords:
CIP2Aandrogen receptorcancer stem-like cellscastration-resistant prostate cancer

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