Study Of Cancer Stem Cells In Colorectal Cancer Progression

Intestinal stem cells(ISC)are critical for tissue homeostasis,tumorigenesis,repair and development.The definition,identification,isolation,and function of ISC has been widely debated for the past decades.Recently,long-term stem cell ex vivo culture has been established,which allows the clarification of the biological nature of ISC.In this dissertation,we discussed the key lingering questions in the field and revealed the functional role of intestinal stem cell in tumor development.LGR5 is leucine-rich repeat containing G protein-coupled receptor(GPCR)and was discovered as a marker for proliferating adult stem cells in small intestine.Here we show LGR5 activates TGFβ signaling in colon cancer cells,enhancing TGFβ-mediated growth inhibition and stress-induced apoptosis.Knockdown of LGR5 attenuates TGFβ signaling,increases cell proliferation,survival and metastasis.In this dissertation,we not only investigated the crosstalk betweent stem cell marker LGR5 and TGFβsignaling pathway,but also provided evidences on developing strategy for the biological therapy of colorectal cancer.