The Function And Mechanism Of Cell Surface Adhesion Protein CNTN1 In Prostate Cancer Cells

According to statistics from WHO in 2020,prostate cancer is the second most common malignant tumor among men in the world,and the fifth most common malignant tumor.Within China,the incidence and mortality of prostate cancer have shown a significant increase in recent years.Although the current clinical treatment methods（including surgery,androgen deprivation,radiotherapy and chemotherapy）have made great progress,prostate cancer is still one of the tumors with the highest mortality.Prostate Cancer Stem Cell（PCSC）is considered to be a key factor in the failure of these conventional treatments.Its existence leads to the recurrence and metastasis of prostate cancer,and the patient has a poor prognosis or even death.Previous research in the laboratory found that the enhancer locus of the risk SNP rs55958994 regulates the phenotype of prostate cancer stem cells.Research has shown that the direct target gene of the enhancer,the cell surface adhesion protein CNTN1,is a key factor in enhancing the phenotype of cancer stem cells;and it was found that the risk SNP rs1041449,rs10486567,and rs55958994 locus e nhancers can regulate CNTN1 gene expression,indicating that CNTN1 is a hub related to many prostate cancer risk SNPs.This research intends to explore the relationship between CNTN1 and prostate cancer stem cells in depth,with a view to revealing the molecular mechanism that it affects the occurrence,development and metastasis of tumors.This research mainly used CRISPR-Cas9 technology to knock out CNTN1 in the prostate cancer cell line 22Rv1.It found that cell cycle arrest in G₂/M phase after CNTN1 knockout,cell proliferation ability,invasion ability,metastasis ability,clone formation ability,stem cell budding ability were weakened,and the ratio of CD44⁺/CD24^-cell subsets decreases.RNA-seq revealed the gene expression regulated by CNTN1,and gene set enrichment analysis（GSEA）of RNA-seq data found that the TGF-βsignaling pathway changed significantly before and after CNTN1 knockout.The EMT process is considered to be one of the important mechanisms for the formation and maintenance of cancer stem cells.The TGF-βsignaling pathway can promote the EMT process through multiple different signaling pathways such as Notch signaling pathway and PI3K/AKT signaling pathway.This study found that after CNTN1 knockout,the expression of tumor stem cells and biomarker molecules of the EMT process would be significantly down-regulated.These findings indicate that CNTN1 can promote the EMT process through the TGF-βsignaling pathway,thereby enhancing the phenotype of PCSCs and promoting the growth and migration of tumor cells.These research results provide valuable theoretical support for the development of prostate cancer treatment methods that target cancer stem cells.