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RASSF1A Tumour Suppressor: Target the Network for Effective Cancer Therapy

Lucía García-Gutiérrez1, Stephanie McKenna1, Walter Kolch1,2,3

  • 1Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.

Cancers
|January 23, 2020
PubMed

Insights

The RASSF1A tumor suppressor

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The RASSF1A protein acts as a crucial scaffold in cell signaling pathways.
  • RASSF1A integrates signals from key regulators of cellular homeostasis like Ras, MST2/Hippo, p53, and death receptors.
  • Loss of RASSF1A expression, often via DNA methylation, is common in solid tumors.

Purpose of the Study:

  • To review the RASSF1A signaling network's modules and their role in cancer.
  • To summarize epigenetic mechanisms causing RASSF1A promoter methylation.
  • To discuss therapeutic strategies for re-establishing RASSF1A function.

Main Methods:

  • Literature review of RASSF1A signaling pathways.
  • Analysis of epigenetic mechanisms (DNA methylation) affecting RASSF1A expression.
  • Review of therapeutic strategies targeting RASSF1A and its network.

Main Results:

  • RASSF1A deregulation is implicated in various cancer types.
  • Epigenetic silencing via DNA methylation is a primary mechanism for RASSF1A loss.
  • The Hippo and RAF1 signaling modules are key components of the RASSF1A network.

Conclusions:

  • Re-expressing RASSF1A or targeting its signaling network offers promising cancer treatment avenues.
  • Multitargeting druggable nodes within the RASSF1A network could yield novel cancer therapies.
  • Understanding RASSF1A's epigenetic regulation is vital for developing effective treatments.
Keywords:
DNMTPRASSF1Aapoptosis and Hippo pathwaycancertherapytumour suppressor

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