Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Am J Physiol Cell Physiol. 2012 May 1;302(9):C1284-92. doi: 10.1152/ajpcell.00318.2011. Epub 2012 Jan 25.
Both caveolin-1 (Cav-1) and Mcl-1 have been implicated in the regulation of cancer cell anoikis, but their relationship and underlying mechanisms of regulation are not known. The present study demonstrated for the first time that Cav-1 regulates Mcl-1 through protein-protein interaction and inhibits its downregulation during cell anoikis in human lung cancer cells. Immunoprecipitation and immunocytochemistry studies showed that Cav-1 interacted with Mcl-1 and prevented it from degradation via the ubiquitin-proteasome pathway. Mcl-1 and Mcl-1-Cav-1 complex were highly elevated in Cav-1-overexpressing cells but were greatly reduced in Cav-1 knockdown cells. Consistent with this finding, we found that Mcl-1 ubiquitination was significantly attenuated by Cav-1 overexpression but increased by Cav-1 knockdown. Together, our results indicate a novel role of Cav-1 in anoikis regulation through Mcl-1 interaction and stabilization, which provides a new insight to the pathogenesis of metastatic lung cancer and its potential treatment.
窖蛋白-1（Cav-1）和 Mcl-1 都被牵涉到了对癌细胞失巢凋亡的调控中，但它们之间的关系和潜在的调控机制尚不清楚。本研究首次表明，Cav-1 通过蛋白-蛋白相互作用来调控 Mcl-1，并在人肺癌细胞的失巢凋亡过程中抑制其下调。免疫沉淀和免疫细胞化学研究表明，Cav-1 与 Mcl-1 相互作用，并通过泛素-蛋白酶体途径防止其降解。Cav-1 过表达细胞中的 Mcl-1 和 Mcl-1-Cav-1 复合物显著升高，而 Cav-1 敲低细胞中的 Mcl-1 和 Mcl-1-Cav-1 复合物则显著降低。与这一发现一致，我们发现 Cav-1 过表达显著减弱了 Mcl-1 的泛素化，而 Cav-1 敲低则增加了 Mcl-1 的泛素化。综上所述，我们的研究结果表明，Cav-1 通过与 Mcl-1 相互作用和稳定化来调控失巢凋亡，这为转移性肺癌的发病机制及其潜在的治疗提供了新的见解。
