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Title

A laminin 511 matrix is regulated by TAZ and functions as the ligand for the alpha6Bbeta1 integrin to sustain breast cancer stem cells

Authors

Cheng Chang, University of Massachusetts Medical SchoolFollow
Hira Lal Goel, University of Massachusetts Medical SchoolFollow
Huijie Gao, University of Massachusetts Medical SchoolFollow
Bryan M. Pursell, University of Massachusetts Medical SchoolFollow
Leonard D. Shultz, The Jackson Laboratory
Dale L. Greiner, University of Massachusetts Medical SchoolFollow
Sulev Ingerpuu, University of Tartu
Manuel Patarroyo, Karolinska Institutet
Shiliang Cao, Dana Farber Cancer Institute
Elgene Lim, Dana Farber Cancer Institute
Junhao Mao, University of Massachusetts Medical SchoolFollow
Karen Kulju. McKee, Robert Wood Johnson Medical School
Peter D. Yurchenco, Robert Wood Johnson Medical School
Arthur M. Mercurio, University of Massachusetts Medical SchoolFollow

UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; Program in Molecular Medicine

Publication Date

2015-01-01

Document Type

Article

Subjects

Breast Neoplasms; Extracellular Matrix; Female; Humans; Integrin alpha6beta1; Laminin; Ligands; Neoplastic Stem Cells; Transcription Factors

Disciplines

Cancer Biology | Cell Biology | Cells | Developmental Biology | Molecular Biology

Abstract

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer.

Rights and Permissions

© 2015 Chang et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

DOI of Published Version

10.1101/gad.253682.114

Source

Genes Dev. 2015 Jan 1;29(1):1-6. doi: 10.1101/gad.253682.114. Link to article on publisher's site

Journal/Book/Conference Title

Genes and development

Related Resources

Link to Article in PubMed

PubMed ID

25561492

Repository Citation

Chang, Cheng; Goel, Hira Lal; Gao, Huijie; Pursell, Bryan M.; Shultz, Leonard D.; Greiner, Dale L.; Ingerpuu, Sulev; Patarroyo, Manuel; Cao, Shiliang; Lim, Elgene; Mao, Junhao; McKee, Karen Kulju.; Yurchenco, Peter D.; and Mercurio, Arthur M., "A laminin 511 matrix is regulated by TAZ and functions as the ligand for the alpha6Bbeta1 integrin to sustain breast cancer stem cells" (2015). Molecular, Cell and Cancer Biology Publications. 22.
https://escholarship.umassmed.edu/mccb_pubs/22