Transcription Factors Slug And KLF5 Affect The Properties Of Hepatocellualr Carcinoma Stem Cell And Drug Resistance

Liver cancer is the fifth most common cancer and the third leading cause of cancer death in the world. The incidence of liver cancer in China accounts for half of that in the world. Although various treatment greatly improves the survival rate of patients with liver cancer, the migration, invasion and resistance to conventional chemotherapy drugs induced by cancer stem cells are the main challenges to the treatment of liver cancer now. Therefore, studying the molecular mechanism of cancer stem cells is significant to intervene and treat liver cancer. Slug was reported as a transcription factor promoting migration and invasion of cancer cells. Cells undergoing EMT obtained the characteristics of cancer stem cells and were able to form metastases after migrating to distant organs. KLF5 protein, also as a transcription factor, was considered to improve cancer cell proliferation and play an important role in maintaining the stem cell properties of embryonic stem cells and intestinal epithelial stem cells. But the effects of Slug and KLF5 on cancer stem cells in hepatocellualr carcinoma is still unclear. By using the method of separating side population, our group sorted cancer stem cells and found that the expression of Slug in them was lower compared to cancer cells while the expression of KLF5 did not obviously decrease. To deeply study the function of Slug and KLF5 in maintaining properties of caner stem cells, we inhibited the expression of Slug and KLF5 and tested cancer stem cell-related biological functions including migration,invasion and drug resistance. The result manifested that inhibition of Slug and KLF5 improved the capability of sphere formation as well as resistance to certain chemothherapies, indicating the promotion of the properties of cancer stem cells.Analysis of molecular mechanism revealed that the inhibition of Slug and KLF5 enhanced the expression of cancer stem cell-related genes, especially the expression of ABC proteins. Otherwise, using the inhibitor of ABC proteins rescued the resistance todrugs caused by knockout of Slug and KLF5 and increased the sensitivity of cancer cell to drugs. Moreover, to research the function of Slug and KLF5 in the progress of EMT,we detected the migratory activity and found KLF5 suppressed cell migration while Slug has no obvious effect on cell migration. Our group revealed the new function of Slug and KLF5 in hepatocellular carcinoma and advised a new approach to studying the molecular mechanisms of liver cancer.