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June 19, 2026Journal of Lipid ResearchOpen Access

KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner

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Authors

NANeha AroraHLHong LiangWKWalaa E. Kattan

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Overview

Randomized trial examines lipid metabolism's effect on Kras mutant activity in cancer cells, suggesting potential therapeutic targeting.

Key Points

  • This research aims to understand how different Kras mutations (G12C and G12D) respond to lipid metabolism uniquely.
  • Analyzed lipid profiles in cells expressing LPCAT1 for their effects on saturated and unsaturated lipids.
  • Conducted electron microscopy to assess nanocluster formation of Kras variants on the plasma membrane.
  • Examined the impact of LPCAT1 knockout on colony formation in Kras mutant-expressing cells.
  • LPCAT1 expression reduced signaling and colony formation in Kras G12D-expressing cells but promoted them in Kras G12C cells.
  • Knocking out LPCAT1 decreased saturated lipids and colony formation in Kras G12C cells.
  • Kras G12C transformed cells exhibited higher levels of saturated lipids compared to Kras G12D cells.

Cite This Study

Arora et al. (2026) studied this question.

synapsesocial.com/papers/6a34dc0f65a5b0777af2c7dfhttps://doi.org/10.1016/j.jlr.2026.101079
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Also Consider

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  1. 1Lysophosphatidylcholine acyltransferase 1 suppresses nanoclustering and function of KRAS2024 · 1 citations
  2. 2Abstract A047: KRAS G12C and G12D mutants exhibit distinct conformational flexibility in the helix 3–switch 2 pocket that drives differential protein function2026
  3. 3Abstract 1655: Targeting lipid metabolism disrupts KRAS oncogenesis in pancreatic cancer2024 · 1 citations
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  5. 5KRASG12R-Mutant Pancreatic Cancer Features Limited ERK/MAPK Transcriptional Activity and a Distinctive Tumor Microenvironment2026 · 3 citations