Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Developmental cell | Nov 20, 2017

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous carcinoma in which various tumor-suppressor genes are lost by mutation, deletion, or silencing. Here we report a tumor-suppressive mode of action for growth-differentiation factor 11 (GDF11) and an unusual mechanism of its inactivation in TNBC. GDF11 promotes an epithelial, anti-invasive phenotype in 3D triple-negative cultures and intraductal xenografts by sustaining expression of E-cadherin and inhibitor of differentiation 2 (ID2). Surprisingly, clinical TNBCs retain the GDF11 locus and expression of the protein itself. GDF11 bioactivity is instead lost because of deficiencies in its convertase, proprotein convertase subtilisin/kexin type 5 (PCSK5), causing inactive GDF11 precursor to accumulate intracellularly. PCSK5 reconstitution mobilizes the latent TNBC reservoir of GDF11 in vitro and suppresses triple-negative mammary cancer metastasis to the lung of syngeneic hosts. Intracellular GDF11 retention adds to the concept of tumor-suppressor inactivation and reveals a cell-biological vulnerability for TNBCs lacking therapeutically actionable mutations.

Pubmed ID: 29161592 RIS Download

Mesh terms: Animals | Bone Morphogenetic Proteins | Cadherins | Cell Line, Tumor | Cell Movement | Cell Proliferation | Female | Growth Differentiation Factors | Humans | Mice | Phenotype | Triple Negative Breast Neoplasms

Research resources used in this publication

Research tools detected in this publication

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: P30 CA044579
  • Agency: NCI NIH HHS, Id: U01 CA215794
  • Agency: NCI NIH HHS, Id: T32 CA009109
  • Agency: NIH HHS, Id: DP2 OD006464
  • Agency: NCI NIH HHS, Id: R01 CA194470

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Addgene

A non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Addgene’s mission is to accelerate research and discovery by improving access to useful research materials and information. We facilitate the sharing of high-quality scientific materials, research reproducibility, and open science by archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Our repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

tool

View all literature mentions

Novus Biologicals

Commercial antibody vendor wich supplies antibodies and other products to life science researchers.

tool

View all literature mentions

lumi

Software that provides an integrated solution for the Illumina microarray data analysis.

tool

View all literature mentions