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Updated: Dec 3, 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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RAS GTPase signalling to alternative effector pathways

Swati Singh1, Matthew J Smith1,2

  • 1Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.

Biochemical Society Transactions
|October 30, 2020
PubMed

Insights

RAS GTPases drive cancer by signaling through effectors like RAF and PI3K. Exploring alternative RAS effectors, such as RALGEFs, RASSF5, and AFDN, may overcome drug resistance in cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • RAS GTPases are crucial for cell development and are frequently mutated in human cancers.
  • RAS oncoproteins promote cancer initiation, progression, and metastasis through constitutive downstream signaling.
  • Current therapies targeting RAF and PI3K pathways are limited by acquired drug resistance.

Purpose of the Study:

  • To explore alternative RAS effector pathways beyond RAF and PI3K.
  • To investigate the biological significance of candidate alternative effectors: RALGEFs, RASSF5, and AFDN.
  • To identify potential new therapeutic targets for RAS-driven cancers.

Main Methods:

  • Review of existing literature on RAS GTPase signaling and effector interactions.
  • Analysis of the roles of RALGEFs, RASSF5, and AFDN in RAS-mediated cellular processes.
  • Discussion of the implications for cancer therapy.

Main Results:

  • RAS GTPases interact with a diverse range of alternative effectors.
  • RALGEFs, RASSF5, and AFDN are identified as key alternative effectors with unexplored roles.
  • These alternative pathways are implicated in cell adhesion, polarity, size, and cytoskeletal organization.

Conclusions:

  • Alternative RAS effector pathways represent promising targets for overcoming drug resistance in RAS-driven cancers.
  • Targeting RALGEFs, RASSF5, and AFDN could offer novel combinatorial therapeutic strategies.
  • Further research into these pathways is warranted given their role in cancer metastasis.
Keywords:
AFDNGTPasesRALGEFRASRASSFeffector

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