胞膜小窩(caveolae)是細(xì)胞質(zhì)膜內(nèi)陷所形成的囊狀結(jié)構(gòu).小窩蛋白(caveolin)是胞膜小窩區(qū)別于其它脂筏結(jié)構(gòu)的特征性蛋白分子,，維持胞膜小窩的結(jié)構(gòu)和功能，包括3個(gè)家族成員小窩蛋白-1,、小窩蛋白-2和小窩蛋白-3,。其中，小窩蛋白-1是參與膽固醇平衡,、分子運(yùn)輸和跨膜信號(hào)發(fā)放事件的主要結(jié)構(gòu)成分,，從而調(diào)節(jié)細(xì)胞的生長(zhǎng)、發(fā)育和增殖,。
小窩蛋白1（Caveolin-1）有促進(jìn)細(xì)胞遷移的作用,，Caveolin-1蛋白表達(dá)的增加與腫瘤進(jìn)展和轉(zhuǎn)移密切有關(guān)。成纖維細(xì)胞中Caveolin-1蛋白的極化和酪氨酸-14的磷酸化對(duì)促進(jìn)腫瘤遷移是必不可少的,。然而,，Caveolin-1對(duì)轉(zhuǎn)移性細(xì)胞的促遷移作用仍然不甚明了,。
近來(lái)發(fā)表在PLoS One雜志上的一則研究，研究人員采用shRNA靶向內(nèi)源性人乳腺癌細(xì)胞MDA-MB-231的Caveolin-1以及B16-F10小鼠黑色素瘤細(xì)胞的異位表達(dá)來(lái)評(píng)估Caveolin-1的促遷移機(jī)制,。抑制MDA-MB-231細(xì)胞的Caveolin-1表達(dá),，乳腺癌細(xì)胞遷移受到抑制，而在B16F10細(xì)胞中Caveolin-1的表達(dá)促進(jìn)黑色素瘤細(xì)胞的遷移,、粘附,。其中機(jī)制涉及酪氨酸-14的磷酸化和RAC-1的激活。（生物谷：Bioon.com）
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.
