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Updated: Apr 1, 2026

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Colorectal cancer-related mutant KRAS alleles function as positive regulators of autophagy

Sara Alves1, Lisandra Castro1, Maria Sofia Fernandes2

  • 1CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

Oncotarget
|September 30, 2015
PubMed

Insights

Mutant KRAS up-regulates autophagy in colorectal cancer (CRC) via the MEK/ERK pathway, promoting cell survival. Autophagy inhibitors may offer a therapeutic strategy for CRC with mutant KRAS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Autophagy's dual role in cancer necessitates tailored therapeutic strategies.
  • RAS isoforms, particularly KRAS, are implicated in autophagy regulation.
  • KRAS mutations are frequent in colorectal cancer (CRC).

Purpose of the Study:

  • To investigate how mutant KRAS alleles regulate autophagy in CRC.
  • To explore the implications of mutant KRAS-mediated autophagy in CRC.
  • To identify potential therapeutic strategies targeting autophagy in CRC.

Main Methods:

  • Established KRAS-humanized yeast and KRAS-non-cancer colon cell models.
  • Assessed the effect of mutated KRAS expression on starvation-induced autophagy.
  • Investigated the role of the MEK/ERK pathway in KRAS-induced autophagy.
  • Examined the contribution of KRAS and autophagy to CRC cell survival during starvation.

Main Results:

  • Mutated KRAS up-regulates starvation-induced autophagy in both colon cell models.
  • KRAS down-regulation inhibited autophagy in CRC cells with KRAS mutations.
  • KRAS-induced autophagy proceeds via MEK/ERK pathway activation.
  • KRAS and autophagy enhance CRC cell survival under starvation conditions.

Conclusions:

  • Mutant KRAS drives autophagy in CRC through the MEK/ERK pathway.
  • Targeting autophagy could be a viable therapeutic approach for CRC patients with KRAS mutations.
  • Autophagy inhibitors may serve as combined or alternative therapies for mutant KRAS CRC.
Keywords:
KRAS mutationsautophagycolorectal cancerhumanized yeastnon-cancer colon cells

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