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Updated: Dec 17, 2025

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
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Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

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A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not

Alexia Hervieu1,2, Sara Farrah Heuss1, Chi Zhang2

  • 1Spatial Signalling Team, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.

Science Signaling
|June 25, 2020
PubMed

Insights

Receptor tyrosine kinases (RTKs) drive cancer. This study reveals Rac1

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Receptor tyrosine kinases (RTKs) like MET are crucial in cancer development and progression.
  • Current models implicate phosphatidylinositol 3-kinase (PI3K) and Rac1 in RTK signaling pathways.
  • Understanding these pathways is key to developing effective cancer therapies.

Purpose of the Study:

  • To elucidate the distinct roles of PI3K and Rac1 in MET-driven cancer.
  • To investigate novel signaling pathways involved in anchorage-independent growth.
  • To identify potential therapeutic targets for overcoming resistance to RTK inhibitors.

Main Methods:

  • Utilized cultured NIH3T3 and glioblastoma cells to study MET signaling.
  • Investigated Rac1's GTPase-dependent and -independent functions.
  • Examined the interaction between Rac1, mTOR, and cellular processes.
  • Assessed the efficacy of mTOR inhibition using rapamycin in mouse models.

Main Results:

  • Class I PI3K mediated MET-induced cell migration but not anchorage-independent growth.
  • Rac1 regulated cell migration via GTPase activity and anchorage-independent growth independently of PI3K.
  • Rac1's adaptor function, through its RKR motif, facilitated mTOR translocation and promoted anchorage-independent growth.
  • mTOR inhibition with rapamycin suppressed tumor growth in MET-mutant and resistant cell grafts.

Conclusions:

  • Discovered a PI3K-independent MET-to-mTOR pathway mediated by Rac1's GTPase-independent function.
  • Rac1 plays a dual role in MET signaling, affecting both migration and anchorage-independent growth.
  • Targeting the Rac1-mTOR pathway offers a potential strategy to overcome resistance to RTK inhibitors in cancer treatment.

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