The Mechanism Of Caveolin-1 Regulating Tumor Cell Geometry And Self-renewal

The geometrical morphological characteristics of cells in living organisms are unique due to their diverse locations and functions.Therefore,the maintenance of these geometrical morphological features is closely related to the normal physiological functions,acquisition of new functions or pathological changes(especially tumors)of cells.During the transformation of normal cells into cancer cells,their biological characteristics and geometrical morphological traits undergo a series of changes to meet the demands of cancer cells.Consequently,cell geometry plays a crucial regulatory role in the behavior and properties of tumor cells.Cav-1,the primary structural protein and regulator of caveolae,is involved in various physiological processes of cells and closely related to the occurrence,development and prognosis of tumors.Previous studies have found that Cav-1 is an essential regulatory factor in the tumor process,involved in regulating tumor cell migration,invasion and proliferation,accompanied by cell morphological reconstruction.However,it remains unclear whether regulating tumor cell geometrical morphology is necessary for Cav-1 to participate in modulating tumor cell phenotype and behavior,and whether cell morphological changes caused by biochemical signals and physical constraints can also produce regulatory effects through cell mechanical signal transduction.Therefore,the aim of this study is to explore the molecular mechanism by which Cav-1 restructures the geometrical morphological characteristics of tumor cells to influence tumor cell self-renewal,clarify the biomechanical mechanism by which biochemical signals regulate tumor cell phenotype and behavior through cell morphological reconstruction,and provide new targets for tumor treatment.In the study,MDA-MB-231 triple negative breast cancer cells with high Cav-1expression were used as the research subjects.First,the effect of Cav-1 on tumor cell morphology was investigated.It was found that after Cav-1 knockout,cell morphology changed significantly,including cell elongation,decreased lamellipodia,and decreased cytoskeleton,especially stress fibers.Further exploring the mechanism by which Cav-1regulates cell morphological changes found that Cav-1 can regulate the activity of small GTPases through the FAK-Rho signaling pathway,stabilize lamellipodia and stress fiber structures,and maintain tumor cell phenotype.Furthermore,this study analyzed the effect of Cav-1 on the self-renewal of MDA-MB-231 cells.It was found that Cav-1 is essential for tumor cells to maintain their self-renewal ability.By limiting cell morphology with microcontact printing technology,it was found that Cav-1 knockout did not affect the self-renewal ability of cells,further confirming that Cav-1 influences the self-renewal ability of tumor cells in a morphology-dependent manner.In addition,Cav-1-dependent maintenance of tumor cell self-renewal ability is controlled by transcriptional level regulation mediated by stemness-related transcription factors(Sox2,etc.),and nuclear deformation under compression can affect gene expression by influencing chromatin distribution in the nucleus.In summary,this study found that Cav-1 can activate small GTPases through the FAK-Rho signaling pathway,thereby maintaining cytoskeleton structure and lamellipodia formation.After Cav-1 knockout in tumor cells,the cytoskeleton decreased,the morphological structure phenotype became more elongated,the nuclear force situation and nuclear morphology changed,thus affecting the expression of transcription factors and reducing the self-renewal ability of cells.