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

被引:118
作者
Chang, Cheng [1 ]
Goel, Hira Lal [1 ]
Gao, Huijie [1 ]
Pursell, Bryan [1 ]
Shultz, Leonard D. [2 ]
Greiner, Dale L. [3 ]
Ingerpuu, Sulev [4 ]
Patarroyo, Manuel [5 ]
Cao, Shiliang [6 ]
Lim, Elgene [6 ]
Mao, Junhao [1 ]
Mckee, Karen Kulju [7 ]
Yurchenco, Peter D. [7 ]
Mercurio, Arthur M. [1 ]
机构
[1] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
[3] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA
[4] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia
[5] Karolinska Inst, Dept Dent Med, SE-17177 Stockholm, Sweden
[6] Dana Farber Canc Inst, Boston, MA 02284 USA
[7] Robert Wood Johnson Med Sch, Dept Pathol, Piscataway, NJ 08854 USA
基金
美国国家卫生研究院;
关键词
TAZ; cancer stem cell; extracellular matrix; integrin; laminin; PATHWAY; YAP;
D O I
10.1101/gad.253682.114
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 alpha 6B beta 1 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 alpha 5 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.
引用
收藏
页码:1 / 6
页数:6
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