Id Proteins Promote a Cancer Stem Cell Phenotype in Mouse Models of Triple Negative Breast Cancer via Negative Regulation of Robo1.
Full text not available from this repository.Item Type: | Article |
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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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