KIBRA promotes prostate cancer cell proliferation and motility

FEBS J. 2016 May;283(10):1800-11. doi: 10.1111/febs.13718. Epub 2016 Apr 5.

Abstract

KIBRA is a regulator of the Hippo-yes-associated protein (YAP) pathway, which plays a critical role in tumorigenesis. In the present study, we show that KIBRA is a positive regulator in prostate cancer cell proliferation and motility. We found that KIBRA is transcriptionally upregulated in androgen-insensitive LNCaPC4-2 and LNCaP-C81 cells compared to parental androgen-sensitive LNCaP cells. Ectopic expression of KIBRA enhances cell proliferation, migration and invasion in both immortalized and cancerous prostate epithelial cells. Accordingly, knockdown of KIBRA reduces migration, invasion and anchorage-independent growth in LNCaP-C4-2/C81 cells. Moreover, KIBRA expression is induced by androgen signaling and KIBRA is partially required for androgen receptor signaling activation in prostate cancer cells. In line with these findings, we further show that KIBRA is overexpressed in human prostate tumors. Our studies uncover unexpected results and identify KIBRA as a tumor promoter in prostate cancer.

Keywords: AR signaling; KIBRA; motility; proliferation; prostate cancer.

Publication types

  • Editorial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgens / physiology
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Gene Knockdown Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Male
  • Neoplasm Invasiveness
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / metabolism
  • Signal Transduction
  • Up-Regulation

Substances

  • Androgens
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Receptors, Androgen
  • WWC1 protein, human