PLoS One：小窝蛋白1促进肿瘤侵袭转移

胞膜小窝(caveolae)是细胞质膜内陷所形成的囊状结构.小窝蛋白(caveolin)是胞膜小窝区别于其它脂筏结构的特征性蛋白分子，维持胞膜小窝的结构和功能，包括3个家族成员小窝蛋白-1、小窝蛋白-2和小窝蛋白-3。其中，小窝蛋白-1是参与胆固醇平衡、分子运输和跨膜信号发放事件的主要结构成分，从而调节细胞的生长、发育和增殖。

小窝蛋白1（Caveolin-1）有促进细胞迁移的作用，Caveolin-1蛋白表达的增加与肿瘤进展和转移密切有关。成纤维细胞中Caveolin-1蛋白的极化和酪氨酸-14的磷酸化对促进肿瘤迁移是必不可少的。然而，Caveolin-1对转移性细胞的促迁移作用仍然不甚明了。

近来发表在PLoS One杂志上的一则研究，研究人员采用shRNA靶向内源性人乳腺癌细胞MDA-MB-231的Caveolin-1以及B16-F10小鼠黑色素瘤细胞的异位表达来评估Caveolin-1的促迁移机制。抑制MDA-MB-231细胞的Caveolin-1表达，乳腺癌细胞迁移受到抑制，而在B16F10细胞中Caveolin-1的表达促进黑色素瘤细胞的迁移、粘附。其中机制涉及酪氨酸-14的磷酸化和RAC-1的激活。

doi:10.1371/journal.pone.0033085
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Caveolin-1-enhanced motility and focal adhesion turnover require tyrosine-14 but not accumulation to the rear in metastatic cancer cells.

Urra H, Torres VA, Ortiz RJ, Lobos L, Díaz MI, Díaz N, H?rtel S, Leyton L, Quest AF.

Caveolin-1 is known to promote cell migration, and increased caveolin-1 expression is associated with tumor progression and metastasis. In fibroblasts, caveolin-1 polarization and phosphorylation of tyrosine-14 are essential to promote migration. However, the role of caveolin-1 in migration of metastatic cells remains poorly defined. Here, caveolin-1 participation in metastatic cell migration was evaluated by shRNA targeting of endogenous caveolin-1 in MDA-MB-231 human breast cancer cells and ectopic expression in B16-F10 mouse melanoma cells. Depletion of caveolin-1 in MDA-MB-231 cells reduced, while expression in B16-F10 cells promoted migration, polarization and focal adhesion turnover in a sequence of events that involved phosphorylation of tyrosine-14 and Rac-1 activation. In B16-F10 cells, expression of a non-phosphorylatable tyrosine-14 to phenylalanine mutant failed to recapitulate the effects observed with wild-type caveolin-1. Alternatively, treatment of MDA-MB-231 cells with the Src family kinase inhibitor PP2 reduced caveolin-1 phosphorylation on tyrosine-14 and cell migration. Surprisingly, unlike for fibroblasts, caveolin-1 polarization and re-localization to the trailing edge were not observed in migrating metastatic cells. Thus, expression and phosphorylation, but not polarization of caveolin-1 favor the highly mobile phenotype of metastatic cells.