The Molecular Mechanism Of PC-1 Promoting Prostate Cancer Metastasis

Prostate cancer(PCa)is the most common male malignancy in Western countries.2022 saw an increase in the number of new cases of prostate cancer to 125,646 and an increase in the number of deaths to 56,239 in China.Therefore,an in-depth study of the molecular mechanisms mediating prostate cancer metastasis is essential for the development of new therapeutic approaches.The PC-1 gene,a prostate cancer-associated gene that we screened in prostate cancer cells using DNA microarray technology,is specifically expressed in malignant prostate cancer tissues and is highly expressed in androgen-independent C4-2 cells and lowly expressed in androgen-dependent LNCa P cells,and its expression level is positively correlated with the malignant progression of prostate cancer cells.The expression level is positively correlated with the malignant progression of prostate cancer cells.In recent years,PC-1has been found to promote the malignant process of prostate cancer,suggesting that PC-1gene may play an important role in prostate cancer metastasis,however,its molecular mechanism remains unclear.In order to explore the role of PC-1 in prostate cancer metastasis and its potential molecular mechanisms.We firstly constructed prostate cancer cell lines with high expression of PC-1 in LNCa P cells and knocked down PC-1 in C4-2 cells to obtain stable overexpression and knockdown of PC-1.The results showed that PC-1 enhanced the migration ability of low malignant prostate cancer LNCa P cells by scratching and transwell assays,and the specific knockdown of PC-1 in high malignant prostate cancer C4-2 cells significantly reduced the migration ability of the cells,suggesting that PC-1may be an important promoter of prostate cancer metastasis.To further explore the molecular mechanism of PC-1 promoting prostate cancer metastasis,we used immunoprecipitation to detect protein-protein interactions,immunofluorescence staining to detect PC-1 affecting the localization of integrin β1 adhesion spots;scratch assay and transwell assay to detect the migratory ability of integrin β1 inhibitory antibody AIIB2 cells and the inhibitory effect of CDK5 inhibitor In addition,in vivo observation of prostate cancer cells with different PC-1 expressions in bone was performed.Clinical specimens were analysed for PC-1,integrin β1 and correlation with prostate cancer metastasis in tissues from prostate cancer patients.Finally,we found that PC-1 is involved in the regulation of prostate cancer cell motility and is closely related to prostate cancer metastasis,and is an important promoter of prostate cancer invasion and metastasis.The study demonstrated that PC-1 controls the interaction between FLNA,Talin1 and integrin β1,and through this interaction assists in the recruitment of FLNA to adherent spots,thereby regulating the localization and activation of integrins in adherent spots,promotes the activation of integrin β1 through the activation of the Cdk5/p35/Talin1 signalling pathway,and induces microfilament reassembly,assembly and depolymerization of adherent spots through the activation of integrin β1,thereby regulates prostate cancer cell motility and metastasis.The use of integrin β1 inhibitory antibodies AIIB2 and Cdk inhibitors had a good inhibitory effect on tumour metastasis in PC-1 high expression.Correlation analysis of clinical specimens showed a significant correlation between primary or metastatic tumours and PC-1 and integrin β1 expression,confirming that PC-1 is indeed closely associated with metastasis in prostate cancer patients.In addition,in vivo experiments in mice confirmed that prostate cancer cells with high PC-1 expression are more likely to form bone metastases.Based on these findings,the PC-1 pathway may become a possible therapeutic target for metastatic prostate cancer,which will provide new ideas to improve the treatment outcome and prognosis of patients with malignant prostate cancer with high PC-1 expression,and provide a theoretical basis for the development of effective individualized treatment plans.