Colorectal cancer (CRC) is a common malignant tumor of digestive system, and its incidence rate and mortality rate ranks the third among malignant tumors [1]. According to the statistics of China Cancer Center, the incidence rate of CRC in China accounts for 24.3% of the world, and the mortality rate accounts for 22.9% of the world which is increasing year by year [2]. At present, the treatment of CRC is mainly surgery combined with radiotherapy, chemotherapy, gene therapy or molecular targeted therapy. However, the 5-year overall survival rate of CRC is still less than 50% [3,4]. CRC has become a serious threat to human health. Therefore, studying the key regulatory molecules in the pathogenesis of CRC and revealing their mechanisms have important theoretical value for the prevention and treatment of CRC.

Recent studies have shown that the occurrence, development, recurrence and metastasis of tumors are closely related to the microenvironment of tumors [5], and hypoxia is one of the most important microenvironment characteristics of tumors [6]. Hypoxia environment is common in solid tumor tissue, and hypoxia is one of the initiating factors of malignant tumor progression [7,8]. A large number of in vitro experiments have shown that hypoxia can promote the invasion and metastasis of tumor cells and the epithelial mesenchymal process of tumor cells [9,10]. Under aerobic conditions, glycolysis of normal cells is inhibited, mainly using aerobic respiration. However, hypoxia in the tumor microenvironment leads to the promotion of glycolysis of tumor cells. In fact, Warburg et al. [11] pointed out that even in the case of sufficient oxygen supply, tumor cells still prefer glycolysis to obtain energy, rather than oxidative phosphorylation with higher energy supply efficiency. This phenomenon is called Warburg effect. Warburg effect was demonstrated to not only provide a large amount of adenine nucleoside triphosphate for the growth and proliferation of tumor cells, but also lead to the production of a large amount of lactate [12]. Histone lactylation is a newly discovered histone modification [13]. Recent studies have found that lactate can participate in the regulation of many gene expressions through the apparent modification of histone lactylation [14,15]. Therefore, the discovery of lactylation provides a new idea for the molecular mechanism of Warburg effect in various tumors.

β-Catenin is a multifunctional protein with dual functions of cell adhesion and signal transduction, which widely exists in various cells, such as endothelial cells, fibroblasts, osteoblasts, and participates in the proliferation, differentiation, apoptosis and other physiological processes of the above cells [16,17]. With the continuous research on malignant mesenchymal tumors and the deepening of the understanding of β-catenin, it is found that β-catenin, as a classic oncogene, is closely related to the occurrence, development, invasion, metastasis and other biological malignant behaviors of most tumors, and could be used as a prognosis marker [18,19]. However, it is still unclear whether hypoxia induction will promote β-catenin lactylation to enhance its protein stability, and thus aggravate the malignant behavior of CRC. Therefore, this research simulated the hypoxic microenvironment of tumor to analyze the specific mechanism of the β-catenin lactylation on the glycolysis and cell stemness of CRC cells.