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Targeting RAS - will GPR31 deliver us a new path forward?

Nicole Fehrenbacher1, Mark R Philips1

  • 1Perlmutter Cancer Center, New York University School of Medicine, New York, NY.

Molecular & Cellular Oncology
|December 7, 2017
PubMed

Insights

Targeting mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) is key for cancer therapy. G protein-coupled receptor 31 (GPR31) mediates KRAS membrane association, offering a new therapeutic target for KRAS-dependent cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Effective therapies targeting oncogenic Kirsten rat sarcoma viral oncogene homolog (RAS) are crucial for cancer treatment.
  • Mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) drives tumorigenesis by associating with the plasma membrane (PM).

Purpose of the Study:

  • To identify novel therapeutic targets for KRAS-dependent cancers.
  • To investigate the role of G protein-coupled receptor 31 (GPR31) in KRAS-driven tumorigenesis.

Main Methods:

  • Investigated the association between GPR31 and KRAS.
  • Assessed the impact of GPR31 on KRAS-dependent cancer cell proliferation, survival, and macropinocytosis.

Main Results:

  • G protein-coupled receptor 31 (GPR31) was identified as a mediator of KRAS membrane association.
  • GPR31 is essential for the proliferation, survival, and macropinocytosis of KRAS-dependent cancer cells.

Conclusions:

  • GPR31 plays a critical role in sustaining KRAS-dependent cancers.
  • GPR31 represents a promising druggable target for developing novel anti-RAS therapies.
Keywords:
CancerG-protein coupled receptor 31GPR31KRASRASanti-RAS therapycancer therapy

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