Id Proteins Promote a Cancer Stem Cell Phenotype in Mouse Models of Triple Negative Breast Cancer via Negative Regulation of Robo1

Id Proteins Promote a Cancer Stem Cell Phenotype in Mouse Models of Triple Negative Breast Cancer via Negative Regulation of Robo1.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.3389/fcell.2020.00552
Journal or Publication Title: Frontiers in Cell and Developmental Biology
Volume: 8
Date: 2020
Divisions: Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.3389/fcell.2020.00552
ISSN: 2296-634X
Date Deposited: 04 Jan 2021 00:31
Abstract:

Breast cancers display phenotypic and functional heterogeneity and several lines of evidence support the existence of cancer stem cells (CSCs) in certain breast cancers, a minor population of cells capable of tumor initiation and metastatic dissemination. Identifying factors that regulate the CSC phenotype is therefore important for developing strategies to treat metastatic disease. The Inhibitor of Differentiation Protein 1 (Id1) and its closely related family member Inhibitor of Differentiation 3 (Id3) (collectively termed Id) are expressed by a diversity of stem cells and are required for metastatic dissemination in experimental models of breast cancer. In this study, we show that ID1 is expressed in rare neoplastic cells within ER-negative breast cancers. To address the function of Id1 expressing cells within tumors, we developed independent murine models of Triple Negative Breast Cancer (TNBC) in which a genetic reporter permitted the prospective isolation of Id1+ cells. Id1+ cells are enriched for self-renewal in tumorsphere assays in vitro and for tumor initiation in vivo. Conversely, depletion of Id1 and Id3 in the 4T1 murine model of TNBC demonstrates that Id1/3 are required for cell proliferation and self-renewal in vitro, as well as primary tumor growth and metastatic colonization of the lung in vivo. Using combined bioinformatic analysis, we have defined a novel mechanism of Id protein function via negative regulation of the Roundabout Axon Guidance Receptor Homolog 1 (Robo1) leading to activation of a Myc transcriptional programme.

Creators:
Creators
Email
Teo, Wee S.
UNSPECIFIED
Holliday, Holly
UNSPECIFIED
Karthikeyan, Nitheesh
UNSPECIFIED
Cazet, Aurélie S.
UNSPECIFIED
Roden, Daniel L.
UNSPECIFIED
Harvey, Kate
UNSPECIFIED
Konrad, Christina Valbirk
UNSPECIFIED
Murali, Reshma
UNSPECIFIED
Varghese, Binitha Anu
UNSPECIFIED
Thankamony, Archana P.
UNSPECIFIED
Chan, Chia-Ling
UNSPECIFIED
McFarland, Andrea
UNSPECIFIED
Junankar, Simon
UNSPECIFIED
Ye, Sunny
UNSPECIFIED
Yang, Jessica
UNSPECIFIED
Nikolic, Iva
UNSPECIFIED
Shah, Jaynish S.
UNSPECIFIED
Baker, Laura A.
UNSPECIFIED
Millar, Ewan K. A.
UNSPECIFIED
Naylor, Matthew J.
UNSPECIFIED
Ormandy, Christopher J.
UNSPECIFIED
Lakhani, Sunil R.
UNSPECIFIED
Kaplan, Warren
UNSPECIFIED
Mellick, Albert S.
UNSPECIFIED
O'Toole, Sandra A.
UNSPECIFIED
Swarbrick, Alexander
UNSPECIFIED
Nair, Radhika
UNSPECIFIED
Last Modified: 04 Jan 2021 00:31
URI: https://eprints.centenary.org.au/id/eprint/812

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