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Updated: Jun 16, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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

Published on: July 17, 2019

A PAK-activated linker for EGFR and FAK

Alok Tomar1, David D Schlaepfer

  • 1Department of Reproductive Medicine, University of California, San Diego, Moores Cancer Center, La Jolla, CA 92093, USA.

Developmental Cell
|February 18, 2010
PubMed

Insights

A novel protein isoform, SRC-3Delta4, bridges EGFR and FAK, enhancing breast carcinoma cell migration and metastasis. This discovery offers new insights into cancer cell motility and potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Transmembrane growth factors and integrin receptors form signaling complexes with FAK, a kinase involved in cell motility.
  • Understanding these complexes is crucial for deciphering cancer progression mechanisms.

Purpose of the Study:

  • To investigate the role of specific protein isoforms in mediating cell signaling pathways.
  • To elucidate the mechanism by which SRC-3Delta4 influences breast carcinoma cell migration and metastasis.

Main Methods:

  • The study utilized molecular biology techniques to identify and characterize the SRC-3Delta4 isoform.
  • Investigated the interaction between SRC-3Delta4, EGFR, and FAK using biochemical assays.
  • Assessed the impact of SRC-3Delta4 on cell migration and metastasis in relevant cancer models.

Main Results:

  • A PAK-phosphorylated alternate-spliced isoform of steroid receptor coactivator-3 (SRC-3Delta4) was identified.
  • SRC-3Delta4 was shown to bridge Epidermal Growth Factor Receptor (EGFR) and Focal Adhesion Kinase (FAK).
  • This bridging significantly enhanced breast carcinoma cell migration and metastasis.

Conclusions:

  • SRC-3Delta4 acts as a critical molecular bridge in signaling pathways regulating cell motility.
  • The findings highlight SRC-3Delta4 as a potential therapeutic target for inhibiting breast cancer metastasis.

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