Mechanism Of KLF4 Regulating CD47 Expression In Colorectal Cancer Stem Cells And Macrophages Phagocytosis Of Tumor Stem Cells

Cancer is a serious threat to human life and health all over the world.In China,the incidence and death rate of cancer are still rising,posing a great threat to people's health.Tumor stem cells are a small number of cells in tumor tissue and have been reported in different types of tumors.Moreover,Cancer stem cells(CSCs)play an important role in the process of tumor occurrence,recurrence and metastasis.Recent findings suggest that the molecular and cellular tumor microenvironment in which these cells are located plays a key role in maintaining stem cell properties and in treating drug resistance,and studies have shown increased expression of CD47 in CSCs,but the molecular mechanism by which CD47 expression regulates CSCs remains unclear.CD47 was first identified as a tumor antigen for ovarian cancer in the 1980 s.Since then,CD47 has been found to be expressed in a variety of solid tumors,including acute myeloid leukemia(AML),colorectal cancer,bladder cancer,pancreatic cancer,liver cancer,and stomach cancer.CD47 is also highly expressed in pediatric and adult brain tumors.High expression of CD47 in cancer cells allows them to escape the fate of phagocytosis,even though they also express large amounts of calcinetin(the main inducer of phagocytosis),because the combination of SIRP proteins in macrophages and CD47 inhibits phagocytosis.In this study,we screened KLF4 through luciferase reporter gene to regulate the expression of CD47 protein on the surface of colorectal CSCs.In addition,lowering KLF4 expression in human colorectal CSCs by sh RNA technique resulted in decreased RNA and protein levels of CD47 and further increased phagocytosis of colorectal CSCs by murine bone marrow derived macrophages.Mechanistically,KLF4 was found to bind directly to CD47 promoter,thus promoting CD47 transcriptional expression.In addition,analysis of data sets from multiple colorectal cancer patients showed that CD47 expression was associated with prognosis.In conclusion,KLF4-mediated CD47 expression helps reveal the underlying mechanism of immune escape of colorectal CSCs,which may provide potential targets for immunotherapy of CSCs.