Rab8 GTPase regulates Klotho-mediated inhibition of cell growth and progression by directly modulating its surface expression in human non-small cell lung cancer

Rab8 GTPase 通过直接调节人类非小细胞肺癌中的表面表达来调节 Klotho 介导的细胞生长和进展抑制

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作者:Bo Chen, Shuhong Huang, Thomas R Pisanic Ii, Alejandro Stark, Yong Tao, Bei Cheng, Yue Li, Yunyan Wei, Weihong Zhao, Tza-Huei Wang, Jianqing Wu

Background

The klotho (KL) gene is an anti-aging gene that has recently been shown to also function as a general tumor suppressor. However, there is currently only limited information regarding the potential molecular signals for regulation of Klotho without identifying precise molecular mechanisms or interactions.

Methods

We performed a mass spectrometry (MS) assay to screen candidate proteins complexed with Klotho derived from immunoprecipitation in human non-small cell lung cancer (NSCLC) cells, and identified Rab8 to be the protein that most prominently interacts with Klotho. We further investigated whether Rab8 can regulate trafficking of Klotho and which process it would modulate using surface biotinylation assay, immunofluorescence and fluorescence ratio microscopy. Furthermore, we explored whether Rab8 is involved in Klotho-mediated function in NSCLC, and verified the

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