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Updated: Jul 6, 2026

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

Cripto-1 alters keratinocyte differentiation via blockade of transforming growth factor-beta1 signaling: role in skin

Anjali Shukla1, Yan Ho, Xin Liu

  • 1Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Molecular Cancer Research : MCR
|March 14, 2008
PubMed

Insights

Cripto-1, a protein involved in development, promotes skin tumor growth by blocking TGF-beta1 signaling. This interference alters keratinocyte differentiation, contributing to squamous cancer progression in mice.

Area of Science:

  • Oncology
  • Developmental Biology
  • Cell Biology

Background:

  • Cripto-1 is a growth factor family member crucial for early embryogenesis.
  • It acts as a coreceptor for Nodal and is frequently overexpressed in human tumors.
  • Cripto-1's role in carcinogenesis, particularly in skin cancer, requires further elucidation.

Purpose of the Study:

  • To investigate the role of Cripto-1 in a two-stage mouse skin carcinogenesis model.
  • To determine how Cripto-1 influences keratinocyte proliferation and differentiation.
  • To explore the mechanism by which Cripto-1 affects transforming growth factor (TGF)-beta1 signaling.

Main Methods:

  • Utilized a two-stage mouse skin carcinogenesis model.
  • Treated primary mouse keratinocytes with Cripto-1.
  • Assessed keratin expression (keratin 1 and keratin 8).
  • Investigated TGF-beta1 signaling pathway blockade using ALK5 inhibitor SB431542 and dominant-negative TGF-beta type II receptor.
  • Analyzed TGF-beta1 receptor binding, Smad2/Smad3 phosphorylation, and TGF-beta1-mediated keratinocyte senescence.

Main Results:

  • Cripto-1 was significantly upregulated in tumor promoter-treated skin and benign papillomas.
  • Cripto-1 treatment stimulated keratinocyte proliferation and induced keratin 8 while inhibiting keratin 1 expression.
  • Blockade of TGF-beta1 signaling mimicked Cripto-1's effects on keratinocyte differentiation.
  • Cripto-1 inhibited TGF-beta1 receptor binding, Smad2/Smad3 phosphorylation, and TGF-beta1-induced keratinocyte senescence.

Conclusions:

  • Cripto-1 upregulation is an early event in skin tumor promotion.
  • Cripto-1 interferes with TGF-beta1 signaling, impacting keratinocyte differentiation.
  • This inhibition by Cripto-1 plays a key role in promoting squamous tumor development in the epidermis.

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