Department of Molecular, Cell and Cancer Biology; Program in Molecular Medicine
Breast Neoplasms; Extracellular Matrix; Female; Humans; Integrin alpha6beta1; Laminin; Ligands; Neoplastic Stem Cells; Transcription Factors
Cancer Biology | Cell Biology | Cells | Developmental Biology | Molecular Biology
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.
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© 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
Genes Dev. 2015 Jan 1;29(1):1-6. doi: 10.1101/gad.253682.114. Link to article on publisher's site
Genes and development
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.