CD151 Accelerates Breast Cancer by Regulating α6 Integrin Function, Signaling, and Molecular Organization

摘要: CD151, a master regulator of laminin-binding integrins (alpha(6)beta(4), alpha(6)beta(1), and alpha(3)beta(1)), assembles these into complexes called tetraspanin-enriched microdomains. CD151 protein expression is elevated in 31% human breast cancers even more high-grade (40%) estrogen receptor-negative (45%) subtypes. The latter includes triple-negative (estrogen receptor, progesterone HER2 negative) basal-like tumors. ablation markedly reduced mammary cell migration, invasion, spreading, signaling (through FAK, Rac1, lck) while disrupting epidermal growth factor receptor (EGFR)-alpha(6) integrin collaboration. Underlying defects, redistributed alpha(6)beta(4) subcellularly severed molecular links between In prototypical tumor line, notably delayed progression ectopic orthotopic xenograft models. These results (a) establish that CD151-alpha(6) play functional role progression; (b) emphasize alpha(6) function via linkage the context microdomains; (c) point to potential relevance as high-priority therapeutic target, with relative selectivity (compared integrins) for pathologic rather than normal physiology.