Caveolin-1 Induces Cancer Cell Migration By Regulating Mitochondrial Dynamics

The high metastatic ability of cancer cells is a key influencing factor for the increase in the mortality of patients.The biological function of mitochondria is closely related to the metastatic ability of cancer cells,but its detail mechanisms remain unclear about the role of molecular signaling pathways mediated by mitochondrial dynamics in cancer cell migration.Mitochondria can maintain a constant state of fission and fusion depends on the mitochondrial dynamics.Cancer cells are often accompanied by an imbalance of mitochondrial dynamics.This process is accompanied by the production of mitochondrial ROS(mtROS),which is related to the metastatic ability of cancer cells.Caveolin-1(Cav-1)plays an important role in the formation of the caveolins.It is a membrane lipid raft that can participate in the regulation of key signal molecules in various cell signaling pathways.,especially,it can directly act on the mitochondria,which can regulate the dynamic level of mitochondrial fusion and fisson.However,the specific molecular mechanism of Cav-1 regulating the distribution and morphology of mitochondria in cells is currently unclear.Therefore,the research content mainly includes exploring the molecular mechanism of Cav-1 regulating cancer cell migration through mitochondrial dynamics,and provides a new perspective on understanding breast cancer cell metastasis and breast cancer treatment strategies.To explore the effects of Cav-1 regulating cancer cell migration through mitochondrial dynamics and the underlying mechanism,we take breast cancer MDA-MB-231 cells overexpressing Cav-1 as the main research object and establish Cav-1stable knockdown breast cancer cell line.First,the migration ability of normal human breast epithelial cells(MCF10A),non-invasive human breast cancer cells(MCF7)and MDA-MB-231 were detected by scratch and Transwell experiments.The results showed that the protein expression levels of Cav-1 affected the ability of tumor cells to metastasize.Secondly,immunofluorescence experiments were detected the morphology and subcellular distribution of mitochondria.The results of it showed that after Cav-1silence,the level of mitochondrial fission decreased and the accumulation of mitochondria in the lamollipodia regions of tumor cells decreased,which indicates that the regionalized distribution of mitochondria may be related to the migration ability of cancer cells.Next,the Western Blotting experiment was used to detect the protein expression levels of DRP1 and MFN2.At the same time,immunofluorescence experiment was used to detect the distribution of DRP1 and MFN2 on the mitochondria.It was found that after Cav-1 silence,it promoted the translocation of DRP1 and MFN2 from the cell membrane to the mitochondria,while it did not affect the total protein expression levels of DRP1 and MFN2,and it was found that the silencing of Cav-1 enhanced the co-localization of DRP1 and MFN2 with mitochondria.Using flow cytometry to detect the changes in the levels of mtROS in cells,it was found that after Cav-1 silence,the level of mtROS production was significantly reduced.Finally,the FRET experiment was used to detect the activity of Rac1 GTPase in the cells.After Cav-1 was silenced,the activity of Rac1 GTPase was significantly reduced,indicating that Cav-1 could affect the production of mtROS and the activity of Rac1 GTPase;the Western Blotting experiment was used to detect the protein expression levels of cytoskeleton regulatory proteins,which have led to the discovery that Cav-1 regulates the migration of breast cancer cells through the DRP1/mtROS/Rac1 GTP/Cofilin-1/F-actin signaling pathway.In summary,Cav-1 can induce the production of mtROS by regulating mitochondrial dynamics,thereby promoting the activation of Rac1 GTPase,and its activation up-regulates the protein expression levels of Profilin-1 and phosphorylation expression levels of Cofilin-1,thereby promoting cytoskeletal reorganization.Finally,the cytoskeletal reorganization promotes the formation of lamellipodia,and ultimately promote cancer cell migration.These results indicate that the migration of cancer cells is related to the mitochondrial dynamics induced by Cav-1,which provides a very significant reference for cancer treatment.