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Updated: Jan 26, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
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Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

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CBP/p300 antagonises EGFR-Ras-Erk signalling and suppresses increased Ras-Erk signalling-induced tumour formation in

Taeko Ichise1,2, Nobuaki Yoshida1, Hirotake Ichise1,2

  • 1Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

The Journal of Pathology
|April 7, 2019
PubMed

Insights

CREB-binding protein (CBP) and p300 function as tumor suppressors in skin cells. Reduced CBP/p300 levels promote skin cancer by enhancing EGFR-Ras-Erk signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • CREB-binding protein (CBP) and p300 are known to possess oncogenic properties by cooperating with pro-oncogenic transcription factors.
  • Mutations in CBP/p300 are frequently observed in human cancers, including cutaneous squamous cell carcinomas.
  • The precise mechanism by which CBP/p300 dysfunction contributes to keratinocyte hyperproliferation and tumorigenesis remains unclear.

Purpose of the Study:

  • To investigate the role of CBP/p300 in epidermal development and function using keratinocyte-specific genetic models in mice.
  • To elucidate the molecular mechanisms underlying CBP/p300's influence on keratinocyte proliferation and tumor formation.

Main Methods:

  • Utilized mice with keratinocyte-specific genetic modifications to study CBP/p300 function.
  • Analyzed the impact of reduced CBP/p300 expression on Ras-Erk signaling, EGFR activity, and Mig6 expression.
  • Assessed the combined effect of reduced CBP/p300 and enhanced Ras-Erk signaling on epidermal tumor development.

Main Results:

  • A single copy of Crebbp or Ep300 was sufficient for normal epidermal development.
  • Reduced CBP/p300 expression exacerbated Ras-Erk signaling-induced keratinocyte hyperproliferation.
  • Decreased CBP/p300 levels led to increased EGFR activity and reduced Mig6 expression, promoting epidermal tumor formation in conjunction with heightened Ras-Erk signaling.

Conclusions:

  • CBP/p300 acts as a tumor suppressor in epidermal keratinocytes.
  • CBP/p300 counteracts oncogenic EGFR-Ras-Erk signaling pathways in the skin.
  • Dysfunction of CBP/p300 contributes to skin cancer development by disrupting EGFR regulation.
Keywords:
CBPEGFRErkMig6Rasepidermishyperplasiap300

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