CD151 accelerates breast cancer by regulating α6 integrin function, signaling, and molecular organization

Xiuwei H. Yang, Andrea L. Richardson, Maria I. Torres-Arzayus, Pengcheng Zhou, Chandan Sharma, Alexander R. Kazarov, Milena M. Andzelm, Jack L. Strominger, Myles Brown, Martin E. Hemler

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

CD151, a master regulator of laminin-binding integrins (α 6β4, α6β1, and α3β1), assembles these integrins into complexes called tetraspanin-enriched microdomains. CD151 protein expression is elevated in 31% of human breast cancers and is even more elevated in high-grade (40%) and estrogen receptor-negative (45%) subtypes. The latter includes triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) basal-like tumors. CD151 ablation markedly reduced basal-like mammary cell migration, invasion, spreading, and signaling (through FAK, Rac1, and lck) while disrupting epidermal growth factor receptor (EGFR)-α6 integrin collaboration. Underlying these defects, CD151 ablation redistributed α6β 4 integrins subcellularly and severed molecular links between integrins and tetraspanin-enriched microdomains. In a prototypical basal-like mammary tumor line, CD151 ablation notably delayed tumor progression in ectopic and orthotopic xenograft models. These results (a) establish that CD151-α6 integrin complexes play a functional role in basal-like mammary tumor progression; (b) emphasize that α6 integrins function via CD151 linkage in the context of tetraspanin-enriched microdomains; and (c) point to potential relevance of CD151 as a high-priority therapeutic target, with relative selectivity (compared with laminin-binding integrins) for pathologic rather than normal physiology.

Original languageEnglish
Pages (from-to)3204-3213
Number of pages10
JournalCancer Research
Volume68
Issue number9
DOIs
StatePublished - May 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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