Related Experiment Video

Updated: Feb 18, 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

14.5K

Tumor-Suppressor Inactivation of GDF11 Occurs by Precursor Sequestration in Triple-Negative Breast Cancer

Sameer S Bajikar1, Chun-Chao Wang2, Michael A Borten1

  • 1Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.

Developmental Cell
|November 22, 2017
PubMed

Insights

Growth-differentiation factor 11 (GDF11) suppresses triple-negative breast cancer (TNBC) by maintaining epithelial characteristics. In TNBC, GDF11 is inactivated by a deficient convertase, PCSK5, revealing a potential therapeutic vulnerability.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Triple-negative breast cancer (TNBC) is aggressive and characterized by loss of tumor-suppressor genes.
  • Understanding novel tumor-suppressor mechanisms and inactivation pathways is crucial for TNBC treatment.

Purpose of the Study:

  • To investigate the tumor-suppressive role of growth-differentiation factor 11 (GDF11) in TNBC.
  • To elucidate the mechanism of GDF11 inactivation in TNBC.
  • To explore therapeutic strategies targeting GDF11 inactivation.

Main Methods:

  • 3D cell cultures and intraductal xenografts of TNBC models.
  • Analysis of GDF11 locus and protein expression in clinical TNBC samples.
  • Investigating the role of proprotein convertase subtilisin/kexin type 5 (PCSK5) in GDF11 processing.
  • PCSK5 reconstitution experiments in vitro and in vivo.

Main Results:

  • GDF11 promotes an epithelial, anti-invasive phenotype in TNBC by sustaining E-cadherin and ID2 expression.
  • Clinical TNBCs express GDF11, but its bioactivity is lost due to PCSK5 deficiency, leading to intracellular GDF11 precursor accumulation.
  • Restoring PCSK5 activity in vitro reactivates latent GDF11 and suppresses TNBC lung metastasis in vivo.

Conclusions:

  • GDF11 acts as a tumor suppressor in TNBC through an epithelial-promoting mechanism.
  • Deficiency in the GDF11 convertase PCSK5 is a key mechanism of GDF11 inactivation in TNBC.
  • Targeting PCSK5 to restore GDF11 bioactivity represents a potential therapeutic strategy for TNBC.
Keywords:
scRNA-seqstochastic profilingsystems biologytransforming growth factor-β

More Related Videos

An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation08:48

An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation

Published on: June 30, 2015

8.7K
Spheroid Assay to Measure TGF-β-induced Invasion09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

22.5K

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.9K
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,...
4.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
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...
10.6K