Reversal of melanocytic malignancy by keratinocytes is an E-cadherin-mediated process overriding beta-catenin

Related Experiment Video

Updated: Aug 7, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Gang Li1, Mizuho Fukunaga, Meenhard Herlyn

  • 1The Wistar Institute, Philadelphia, PA 19104, USA.

Experimental Cell Research
|June 15, 2004
PubMed

Insights

Restoring E-cadherin in melanoma cells re-establishes keratinocyte control, inhibiting proliferation. Functional E-cadherin-mediated cell adhesion is crucial for this keratinocyte-mediated regulation of melanoma cells.

Area of Science:

  • Cell Biology
  • Dermatology
  • Cancer Research

Background:

  • Loss of E-cadherin in melanoma cells disrupts normal cellular interactions and control mechanisms.
  • Keratinocytes normally regulate melanoma cell proliferation and phenotype.

Purpose of the Study:

  • To investigate the role of E-cadherin in restoring keratinocyte-mediated control over metastatic melanoma cells.
  • To determine if E-cadherin's function in cell adhesion is necessary for reversing melanoma malignancy.

Main Methods:

  • Introduction of E-cadherin and its derivatives into the metastatic melanoma cell line 1205Lu.
  • Assessment of E-cadherin's functionality in mediating cell adhesion and downregulating MCAM in co-culture.
  • Evaluation of proliferation inhibition and the impact of beta-catenin status.

Main Results:

  • E-cadherin and an E-cadherin-alpha-catenin fusion protein restored cell adhesion and inhibited melanoma proliferation.
  • These functional E-cadherin variants downregulated MCAM in co-culture, irrespective of beta-catenin.
  • A cytoplasmic domain-deleted E-cadherin derivative (E-cadDeltaCYT) failed to reverse malignancy.

Conclusions:

  • E-cadherin-mediated cell adhesion is essential for keratinocyte-mediated control of melanocytic cells.
  • This control mechanism can overcome the proliferative drive associated with beta-catenin activity in melanoma.

More Related Videos

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model12:37

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Published on: September 7, 2013

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

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...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
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...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
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,...