Keeping order in the neighborhood: new roles for TGFbeta in maintaining epithelial homeostasis

Related Experiment Video

Updated: Jul 10, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Lalage M Wakefield1, Christina Stuelten

  • 1Lab of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. lw34g@nih.gov

Cancer Cell
|October 16, 2007
PubMed

Insights

Transforming growth factor-beta (TGF-β) signaling loss in stratified epithelia causes spontaneous squamous cell carcinomas in mouse anogenital regions. This reveals TGF-β

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Transforming growth factor-beta (TGF-β) signaling is implicated in tumor suppression across various organs.
  • Previous studies have not linked TGF-β receptor inactivation to spontaneous tumor development in mouse models.

Purpose of the Study:

  • To investigate the role of the type II TGF-β receptor in stratified epithelia regarding spontaneous tumorigenesis.
  • To determine the specific sites and types of tumors that arise upon loss of TGF-β signaling.

Main Methods:

  • Targeted knockout of the type II TGF-β receptor gene in mouse models.
  • Analysis of spontaneous tumor development in stratified epithelial tissues, specifically comparing anogenital and skin regions.

Main Results:

  • Mice with targeted knockout of the type II TGF-β receptor specifically developed spontaneous squamous cell carcinomas in the anogenital region.
  • No spontaneous tumors were observed in the skin of these mice.
  • Loss of TGF-β signaling destabilized the epithelium, leading to failure of homeostasis under proliferative stress and unmasking of invasive phenotypes.

Conclusions:

  • The type II TGF-β receptor plays a critical role in preventing squamous cell carcinoma in the anogenital region.
  • TGF-β signaling is essential for maintaining epithelial stability and suppressing latent oncogenic phenotypes at this site.

More Related Videos

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing07:05

TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing

Published on: February 26, 2021

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin10:51

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

Published on: July 14, 2017

Related Concept Videos

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Epithelial Tissues and Their Functions01:23

Epithelial Tissues and Their Functions

Epithelial tissues are large sheets of cells covering all of the surfaces of the body. These surfaces can be internal or external, for example, skin, airways, the digestive tract, the urinary system, and the reproductive system. Hollow organs and body cavities that do not connect to the body's exterior, including blood vessels and serous membranes, are lined by epithelial tissue known as the endothelium.
Epithelial tissues provide the body's first line of protection from physical, chemical, and...
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...