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Updated: Feb 27, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

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KIBRA attains oncogenic activity by repressing RASSF1A

Anuj1, Lakshmi Arivazhagan1, Rohan Prasad Surabhi1

  • 1Department of Biotechnology, Indian Institute of Technology Madras (IITM), Chennai 600036, India.

British Journal of Cancer
|July 1, 2017
PubMed
Abstract

Insights

KIBRA protein is upregulated in breast cancer, promoting tumor growth and progression by repressing the tumor suppressor RASSF1A. This study demonstrates KIBRA's in vivo tumor-forming ability and its oncogenic mechanism.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • KIBRA, initially identified as a neuronal protein, is implicated in various cellular functions beyond the nervous system.
  • KIBRA interacts with dynein light chain 1, crucial for estrogen receptor transactivation in breast cancer.
  • KIBRA acts as a substrate for key kinases (Cdk1, Aurora, ERK), regulating cell cycle, proliferation, and migration.

Purpose of the Study:

  • To investigate the role of KIBRA in breast cancer progression.
  • To elucidate the molecular mechanisms underlying KIBRA's potential oncogenic activity.

Main Methods:

  • KIBRA expression analyzed in breast tissues and cell lines using Western blotting, IHC, and RT-PCR.
  • Stable KIBRA overexpression and knockdown cell lines generated to assess transforming properties.
  • In vivo tumorigenic efficacy evaluated through xenograft studies in nude mice.
  • Quantitative PCR array used to identify molecular targets of KIBRA.

Main Results:

  • KIBRA is significantly upregulated in breast cancer cells and tumors, correlating with disease progression.
  • Overexpression of KIBRA enhanced transforming properties in fibroblasts and breast cancer cells, while knockdown reduced them.
  • Fibroblasts overexpressing KIBRA exhibited increased tumor-forming potential in vivo.
  • RASSF1A, a known tumor suppressor, identified as a transcriptional target repressed by KIBRA.

Conclusions:

  • This study provides the first evidence of KIBRA's in vivo tumorigenic capacity.
  • KIBRA promotes cancer cell transformation by repressing the tumor suppressor RASSF1A.
  • KIBRA represents a potential therapeutic target in breast cancer treatment.

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