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Tumor suppressor role of phospholipase C epsilon in Ras-triggered cancers

Marta Martins1, Afshan McCarthy, Rhona Baxendale

  • 1Division of Biosciences, Institute of Structural and Molecular Biology, and Department of Cell and Developmental Biology, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|March 5, 2014
PubMed

Insights

Phospholipase Cε (PLCε) acts as a tumor suppressor in Ras-driven cancers. Its downregulation in tumors suggests PLCε may serve as a valuable cancer biomarker.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Phospholipase Cε (PLCε) is a known Ras effector, but its role in cancer and Ras-mediated tumorigenesis is unclear.
  • Understanding PLCε's function in cancer is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the role of PLCε in Ras-driven cancers.
  • To determine if Ras binding influences PLCε's function in tumorigenesis.
  • To explore PLCε's potential as a cancer biomarker.

Main Methods:

  • Generated Plce knockout (Plce(-/-)) and Ras-binding deficient (Plce(RAm/RAm)) mouse models.
  • Utilized a two-stage skin carcinogenesis protocol to assess tumor susceptibility.
  • Analyzed PLCε expression in LSL-Kras(G12D) nonsmall cell lung carcinoma models and cellular systems.
  • Investigated the impact of lipase activity and protein kinase C enzymes on PLCε's cell growth inhibition.
  • Explored the involvement of histone deacetylase in PLCε downregulation.

Main Results:

  • Plce(-/-) and Plce(RAm/RAm) mice showed increased susceptibility to skin tumors, indicating a tumor suppressor role for PLCε.
  • Ras binding partially regulates PLCε's function in tumorigenesis.
  • PLCε was significantly downregulated in animal tumors and cellular systems expressing oncogenic Ras.
  • PLCε's inhibitory effect on cell growth requires intact lipase activity and involves protein kinase C.
  • Histone deacetylase may contribute to PLCε downregulation.

Conclusions:

  • PLCε possesses a previously unrecognized tumor suppressor function in animal models.
  • Downregulation of PLCε in various tumors suggests its potential utility as a biological marker for cancer.
  • Further research into PLCε's mechanisms in cancer is warranted.

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