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

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.

• Authors: 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
• Journal: Genes & development (Genes Dev) Vol. 29 Issue 1 Pg. 1-6 (Jan 01 2015) ISSN: 1549-5477 [Electronic] United States
• PMID: 25561492 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Chang et al.; Published by Cold Spring Harbor Laboratory Press.

Chemical References

• Integrin alpha6beta1
• Intracellular Signaling Peptides and Proteins
• Laminin
• Ligands
• Trans-Activators
• Transcription Factors
• Transcriptional Coactivator with PDZ-Binding Motif Proteins
• WWTR1 protein, human
• laminin 10

Topics

• Breast Neoplasms (physiopathology)
• Extracellular Matrix (metabolism)
• Female
• Humans
• Integrin alpha6beta1 (metabolism)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Laminin (metabolism)
• Ligands
• Neoplastic Stem Cells (pathology)
• Trans-Activators
• Transcription Factors
• Transcriptional Coactivator with PDZ-Binding Motif Proteins