Related Experiment Video

Updated: Jun 24, 2026

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
10:51

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin

Published on: July 14, 2017

Epidermal growth factor receptor/beta-catenin/T-cell factor 4/matrix metalloproteinase 1: a new pathway for

Christine Jean1, Amandine Blanc, Naïs Prade-Houdellier

  • 1Institut National de la Santé et de la Recherche Médicale, U563, Toulouse cedex-3, France. christine.jean@inserm.fr

Cancer Research
|April 2, 2009
PubMed

Insights

UVA radiation activates epidermal growth factor receptor (EGFR) in skin cells, leading to beta-catenin changes that increase cell invasion and matrix degradation. This process impacts skin repair, photoaging, and skin cancer development.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cell Biology

Background:

  • UV irradiation is known to activate epidermal growth factor receptor (EGFR) in keratinocytes.
  • The specific signaling pathways and cellular consequences of UV-induced EGFR activation are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which UVA radiation activates EGFR in keratinocytes.
  • To investigate the downstream effects of UVA-mediated EGFR activation on beta-catenin signaling and cellular functions.

Main Methods:

  • Investigated UVA-induced tyrosine phosphorylation of beta-catenin at Y654.
  • Examined the dissociation of E-cadherin/alpha-catenin/beta-catenin complexes.
  • Assessed EGFR-dependent and Wnt-independent beta-catenin relocalization to the nucleus.
  • Analyzed the formation of beta-catenin/T-cell factor 4 (TCF4) complexes.
  • Studied the binding of beta-catenin/TCF4 to the matrix metalloproteinase 1 (MMP1) promoter.
  • Measured MMP1 gene and protein expression.
  • Evaluated keratinocyte migration on collagen and gelatin.

Main Results:

  • UVA-induced EGFR activation causes beta-catenin tyrosine phosphorylation at Y654, disrupting cell-to-cell adhesion complexes.
  • UVA triggers EGFR-dependent, Wnt-independent nuclear translocation of beta-catenin.
  • The beta-catenin/TCF4 complex binds to the MMP1 promoter, upregulating MMP1 expression.
  • UVA exposure enhances keratinocyte migration and extracellular matrix degradation via MMP1.

Conclusions:

  • UVA stimulates keratinocyte invasiveness through EGFR-dependent disruption of cell adhesion and promotion of migration.
  • EGFR-mediated regulation of beta-catenin and MMP1 plays a key role in UVA-induced keratinocyte responses.
  • These findings offer insights into skin repair mechanisms and the pathogenesis of photoaging and photocarcinogenesis.

More Related Videos

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates08:19

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates

Published on: April 22, 2019

A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration08:55

A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration

Published on: March 17, 2018

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Renewal of Skin Epidermal Stem Cells01:12

Renewal of Skin Epidermal Stem Cells

The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells,...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Skin Cancer01:30

Skin Cancer

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...