Caveolin-1-enhanced motility and focal adhesion turnover require tyrosine-14 but not accumulation to the rear in metastatic cancer cells.
Caveolin-1-enhanced motility and focal adhesion turnover require tyrosine-14 but not accumulation to the rear in metastatic cancer cells.
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DOI：
10.1371/journal.pone.0033085
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Quest AF
中科院分区：
文献类型：
--
作者：
Urra H;Torres VA;Ortiz RJ;Lobos L;Díaz MI;Díaz N;Härtel S;Leyton L;Quest AF
已知小窝蛋白-1促进细胞迁移，小窝蛋白-1表达增加与肿瘤进展和转移有关。在成纤维细胞中，小窝蛋白-1极化和酪氨酸-14的磷酸化是促进迁移所必需的。然而，小窝蛋白-1在转移细胞迁移中的作用仍不清楚。在这里，通过shRNA靶向内源性小窝蛋白-1在人乳腺癌细胞MDA-MB-231和在B16-F10小鼠黑色素瘤细胞中的异位表达来评估小窝蛋白-1参与转移细胞迁移的作用。MDA-MB-231细胞中小凹蛋白-1的缺失减少，而在B16-F10细胞中的表达促进了一系列涉及酪氨酸-14磷酸化和RAC-1激活的事件的迁移、极化和局部黏附转换。在B16-F10细胞中，一个非磷酸化酪氨酸-14对苯丙氨酸突变体的表达未能概括野生型小窝蛋白-1的作用。或者，用Src家族激酶抑制剂PP2处理MDA-MB-231细胞可以减少小凹蛋白-1对酪氨酸-14的磷酸化和细胞迁移。令人惊讶的是，与成纤维细胞不同，在迁移的转移细胞中没有观察到小窝蛋白-1极化和重新定位到后缘。因此，小窝蛋白-1的表达和磷酸化，而不是极化，有利于转移细胞的高流动性表型。
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.
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影响因子：
5.2
作者：
Bastian, Philipp;Posch, Birte;Entschladen, Frank
通讯作者：
Entschladen, Frank
影响因子：
4.5
作者：
Hill, Michelle M.;Scherbakov, Nadja;Parat, Marie-Odile
通讯作者：
Parat, Marie-Odile
DOI：
10.1083/jcb.200709019
发表时间：
2008-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Nabi IR
影响因子：
11.2
作者：
Joshi, Bharat;Strugnell, Scott S.;Nabi, Ivan R.
通讯作者：
Nabi, Ivan R.
影响因子：
3.3
作者：
Gálvez, BG;Matías-Román, S;Arroyo, AG
通讯作者：
Arroyo, AG