title: 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.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Cheng
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; arthur.mercurio@umassmed.edu hira.goel@umassmed.edu.
authors.forename: Hira Lal
authors.initials: HL
authors.lastname: Goel
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Huijie
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Bryan
authors.initials: B
authors.lastname: Pursell
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA;
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, 50090 Tartu, Estonia;
authors.forename: Sulev
authors.initials: S
authors.lastname: Ingerpuu
authors.affiliation: Department of Dental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden;
authors.forename: Manuel
authors.initials: M
authors.lastname: Patarroyo
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts 02284, USA;
authors.forename: Shiliang
authors.initials: S
authors.lastname: Cao
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts 02284, USA;
authors.forename: Elgene
authors.initials: E
authors.lastname: Lim
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Junhao
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Karen Kulju
authors.initials: KK
authors.lastname: McKee
authors.affiliation: Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Yurchenco
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; arthur.mercurio@umassmed.edu hira.goel@umassmed.edu.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Mercurio
mesh_terms: D001943:Breast Neoplasms / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D039121:Integrin alpha6beta1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008024:Ligands; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: D039121:Integrin alpha6beta1; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D008024:Ligands; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C119013:laminin 10
keywords: TAZ; cancer stem cell; extracellular matrix; integrin; laminin