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Updated: Dec 5, 2025

Generation and Culturing of Primary Human Keratinocytes from Adult Skin
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Generation and Culturing of Primary Human Keratinocytes from Adult Skin

Published on: December 22, 2017

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RasGRP1 induces autophagy and transformation-associated changes in primary human keratinocytes

Lauren L Fonseca1, Won Seok Yang2, Dirk Geerts3

  • 1Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA; Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture, University of Hawaii at Manoa, Honolulu, HI 96822, USA.

Translational Oncology
|October 19, 2020
PubMed

Insights

RasGRP1 protein is elevated in human skin cancer, driving Ras activation and cellular changes. This protein

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Ras mutations are infrequent in human cutaneous squamous cell carcinomas (cSCC), despite widespread Ras pathway activation.
  • RasGRP1, a guanine nucleotide exchange factor, is crucial for Ras activation and mouse cSCC development.
  • The specific role of RasGRP1 in human keratinocyte carcinogenesis is not well understood.

Purpose of the Study:

  • To investigate the role of RasGRP1 in human keratinocyte carcinogenesis.
  • To determine if RasGRP1 expression can induce oncogenic transformation in human skin cells.

Main Methods:

  • Quantification of RasGRP1 expression in human cSCC samples.
  • Analysis of Ras activation, cellular morphology, and autophagy markers (LC3-II, LC3 puncta) in RasGRP1-expressing human primary keratinocytes.
  • Assessment of epithelial stratification in an in vitro organotypic skin model.
  • Evaluation of transformation-like changes in skin cells from Li-Fraumeni patients with p53 mutations.

Main Results:

  • RasGRP1 is significantly elevated in human cSCC.
  • High RasGRP1 expression in keratinocytes activates endogenous Ras, induces morphological changes (vacuoles, growth arrest), and promotes autophagy.
  • RasGRP1-expressing keratinocytes exhibit impaired stratification in an organotypic model.
  • RasGRP1 induces transformation-like changes in p53-deficient skin cells, indicating oncogenic potential.

Conclusions:

  • RasGRP1 plays a significant role in human epidermal keratinocyte carcinogenesis.
  • RasGRP1 represents a potential therapeutic target for human cSCC.

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