Hypoxia induced ?-catenin lactylation promotes the cell proliferation and stemness of colorectal cancer through the wnt signaling pathway

Colorectal cancer (CRC) is a common malignant tumor of digestive system. Its incidence rate and mortality rate ranks the third among all the malignant tumors. The objective of this study was to explore the role of beta-catenin in the CRC progression. The CRC tissues were collected to analyze the beta-catenin levels. The CRC cells (SW620 and RRKO) were treated with hypoxia to simulate the hypoxic microenvironment of tumor in vitro. The beta-catenin levels in the CRC cells were assessed with RT-qPCR, Western blot and Immunofluorescence. The cell biological behaviors were determined with CCK-8, flow cytometry and sphere formation assays. Besides, the glucose uptake, lactate production, ECAR and OCR was detected by seahorse. For the beta-catenin lactylation determination, the IP and Western blot assay was performed. Then the protein stability of beta-catenin was measured after cycloheximide treatment. The results showed that beta-catenin was highly expressed in the CRC tissues and cells. Hypoxia treatment dramatically increased the protein levels and lactylation of beta-catenin in the CRC cells. In addition, beta-catenin knockdown dramatically inhibited the cell growth and stemness of the CRC cells. Besides, activation of Wnt signaling pathway neutralized the role of sh-beta-catenin in the hypoxia treated CRC cells. In conclusion, this study confirmed that hypoxia induced the glycolysis promoted the beta-catenin lactylation, which further enhanced the protein stability and expression of beta-catenin, thus aggravating the malignant behaviors of CRC cells.