A laminin 511 matrix is regulated by TAZ and functions as the ligand for the α6Bβ1 integrin to sustain breast cancer stem cells

Cheng Chang; Hira Lal Goel; Huijie Gao; Bryan Pursell; Leonard D. Shultz; Dale L. Greiner; Sulev Ingerpuu; Manuel Patarroyo; Shiliang Cao; Elgene Lim; Junhao Mao; Karen Kulju McKee; Peter D. Yurchenco; Arthur M. Mercurio

doi:10.1101/gad.253682.114

A laminin 511 matrix is regulated by TAZ and functions as the ligand for the α6Bβ1 integrin to sustain breast cancer stem cells

¹Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
²The Jackson Laboratory, Bar Harbor, Maine 04609, USA;
³Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
⁴Institute of Molecular and Cell Biology, University of Tartu, 50090 Tartu, Estonia;
⁵Department of Dental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden;
⁶Dana Farber Cancer Institute, Boston, Massachusetts 02284, USA;
⁷Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA

Corresponding authors: arthur.mercurio{at}umassmed.edu, hira.goel{at}umassmed.edu

↵9 These authors contributed equally to this work.

↵8 Present address: Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.

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 α6Bβ1 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 α5 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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Footnotes

Supplemental material is available for this article.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.253682.114.

Received October 10, 2014.
Accepted November 21, 2014.

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