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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Both sides of the same coin: Rac1 splicing regulating by EGF signaling

Xiang-Dong Fu1

  • 1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.

Cell Research
|February 11, 2017
PubMed

Insights

Epidermal Growth Factor (EGF) triggers cancer cell migration by inducing ubiquitylation of hnRNP A1 and altering Rac1 splicing. This highlights converging EGF signals on splicing regulators to promote cancer pathways.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Epidermal Growth Factor (EGF) is a known mitogen that stimulates cancer cell proliferation.
  • Alternative splicing plays a critical role in cancer progression and cell motility.
  • Splicing regulators, such as hnRNP A1 and SR proteins, are key targets in understanding cancer pathways.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which EGF enhances cancer cell migration.
  • To investigate the role of E3 ubiquitin ligase adaptor SPSB1 in EGF-mediated signaling.
  • To understand how EGF signaling converges on splicing regulators to influence alternative splicing of Rac1.

Main Methods:

  • Investigated the induction of SPSB1 by EGF in cancer cells.
  • Examined the recruitment of Elongin B/C-Collin complex by SPSB1.
  • Analyzed the ubiquitylation of hnRNP A1.
  • Assessed the synergistic effects of EGF-activated SR proteins on alternative splicing.
  • Studied the impact on Rac1 alternative splicing and cell migration.

Main Results:

  • EGF induces the expression of E3 ubiquitin ligase adaptor SPSB1.
  • SPSB1 recruits the Elongin B/C-Collin complex, leading to hnRNP A1 ubiquitylation.
  • EGF signaling synergizes with SR proteins to alter Rac1 alternative splicing.
  • These coordinated events enhance cancer cell migration.

Conclusions:

  • EGF signaling converges on both negative (hnRNP A1) and positive (SR proteins) splicing regulators.
  • This convergence promotes a key cancer pathway by enhancing cell migration through altered Rac1 splicing.
  • SPSB1-mediated ubiquitylation of hnRNP A1 is a critical step in EGF-driven cancer cell motility.

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