Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells

BMC Cancer
Juan ZengHuawei Zou

Abstract

Activation of c-Met, a receptor tyrosine kinase, induces radiation therapy resistance in non-small cell lung cancer (NSCLC). The activated residual of c-Met is located in lipid rafts (Duhon et al. Mol Carcinog 49:739-49, 2010). Therefore, we hypothesized that disturbing the integrity of lipid rafts would restrain the activation of the c-Met protein and reverse radiation resistance in NSCLC. In this study, a series of experiments was performed to test this hypothesis. NSCLC A549 and H1993 cells were incubated with methyl-β-cyclodextrin (MβCD), a lipid raft inhibitor, at different concentrations for 1 h before the cells were X-ray irradiated. The following methods were used: clonogenic (colony-forming) survival assays, flow cytometry (for cell cycle and apoptosis analyses), immunofluorescence microscopy (to show the distribution of proteins in lipid rafts), Western blotting, and biochemical lipid raft isolation (purifying lipid rafts to show the distribution of proteins in lipid rafts). Our results showed that X-ray irradiation induced the aggregation of lipid rafts in A549 cells, activated c-Met and c-Src, and induced c-Met and c-Src clustering to lipid rafts. More importantly, MβCD suppressed the proliferation of A549 and H1993...Continue Reading

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Citations

Nov 8, 2018·Expert Review of Proteomics·Ahmed MohamedMichelle M Hill
Jul 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Meran Keshawa EdiriweeraSomi Kim Cho
Sep 15, 2019·Journal of Experimental & Clinical Cancer Research : CR·Xiao DingSong Li
Jan 17, 2021·International Journal of Molecular Sciences·Michela CodiniElisabetta Albi
Feb 3, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Andy GöbelTilman D Rachner
Jul 23, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Huanji XuFeng Bi

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Methods Mentioned

BETA
electrophoresis
X-ray
flow cytometry
fluorescence microscopy
density gradient centrifugation
density

Software Mentioned

- Pro - Analyzer
GraphPad Prism
BD Accuri C6
Gel

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