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Updated: Jun 24, 2025

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Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer

Jennifer E Klomp1, J Nathaniel Diehl2, Jeffrey A Klomp1,3

  • 1Lineberger Comprehensive Cancer Center; University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Science (New York, N.Y.)
|June 6, 2024
PubMed

Insights

This study reveals how ERK1 and ERK2 kinases drive KRAS-mutant pancreatic cancer. Researchers mapped ERK-dependent proteins, uncovering new functions for ERK in cancer progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Mutant KRAS drives pancreatic cancer growth.
  • ERK1 and ERK2 (extracellular signal-regulated kinases) are key signaling molecules implicated in cancer.

Purpose of the Study:

  • To elucidate the mechanisms by which ERK1 and ERK2 support mutant KRAS-driven pancreatic cancer.
  • To identify the ERK-dependent phosphoproteome in KRAS-mutant pancreatic cancer.

Main Methods:

  • Phosphoproteomic analysis of KRAS-mutant pancreatic cancer cells.
  • Identification and characterization of ERK-dependent phosphosites and proteins.

Main Results:

  • ERK1 and ERK2 share similar signaling and transforming outputs.
  • The KRAS-regulated phosphoproteome is predominantly controlled by ERK.
  • Identified 4666 novel ERK-dependent phosphosites on 2123 proteins, expanding the known ERK signaling network.
  • ERK controls a dynamic phosphoproteome impacting cyclin-dependent kinase regulation and RHO GTPase function.

Conclusions:

  • ERK signaling is central to KRAS-mutant pancreatic cancer.
  • This study provides a comprehensive molecular map of ERK's role in driving pancreatic cancer growth.
  • Revealed a more complex function for ERK in cancer than previously understood.

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