SMC1A Recruits Tumor-associated-Fibroblasts(TAFs) And Promotes Colorectal Cancer Metastasis

Tumor-associated-fibroblasts(TAFs)are the most important host cells in the stroma and take part in extracellular matrix construction and cancer colony development.During cancer colonization,seed cells from primary tumor can reconstruct the microenvironment by recruiting circulating cancer cells and TAFs to the metastasis site.Previous studies have established that SMC1A,a subunit of cohesin,is an important trigger signal for liver metastasis in colorectal cancer.We investigated the particular effects as well as the underlying mechanism of SMC1A on TAFs recruitment during liver metastasis of colorectal cancer.Here,We found that:first,the high expression of SMC1A in colorectal cancer cells promotes the invasiveness and the viability of these cells by recruiting circulating TAFs,facilitating early tumor con-struction and tumorigenesis;second,different expression levels of SMC1A influenced the reformation of fibroblasts,which assisted tumorigenesis,and third,expression of SMC1A stimulated the secretion of the inflammatory mediators of TNF-? and IL-1b,and up-regulated the transcriptional expression of MMP2 and VEGF-b,both of which were involved in the tumor-related gene pathway.Objective:To study the interaction between tumor cells and microenvironmental TAFs during colonic metastasis and to explore the relationship between the proliferation of tumor cells and the activation of TAFs in metastatic host environment.Methods:To observe whether the expression of SMC1A in colorectal cancer cells could affect the recruitment of colon cancer TAFs in the process of metastasis by establishing an animal model in which multiple levels of intervention and cross recruitment experiments were designed.Find out how colon cancer cells activate and recruit TAFs and the related cytokines in this process.Results:First,high expression of SMC1A colon cancer cells,showing a stronger invasive and viability.Second,the corresponding TAFs of high SMC1A expression showed a stronger aggressive and metastatic potential.Thirdly,SMC1A overexpressing colon cancer cells secrete more TNF-? and IL-1?,while up-regulating the expression of MMP2 and VEGF-? transcripts associated with tumor-associated gene pathways.Conclusion:SMC1A plays an important role in cancer cell proliferation and metastasis.The high expression of SMC1A in colorectal cancer cells can promote cell invasiveness and viability.Circulating TAFs are involved in the construction of distant metastasis.In the present study,we found that the elevated expression of SMC1A in colorectal cancer cells promoted liver metastasis by recruiting the circulating TAFs to facilitate prophase tumor construction and tumorigenicity.We also found that a potential molecular mechanism underlying colorectal cancer metastasis might be that higher SMC1A expression of promoted metastasis through the elevated secretion of the inflammatory mediators TNF-? and IL-1b,and the increased expression of the tumor-related pathway genes MMP2 and VEGF-b.