Lactic acid in tumor invasion

Invasion involves tumor cells altering their cell-matrix interactions and acquiring motility for metastatic spread. Invasive tumor cells exhibit dysregulated metabolism and enhanced aerobic glycolysis, leading to nutrient depletion, hypoxia, and lactic acid production. Lactic acid is a byproduct of glycolysis capable of promoting oncogenic progression, but its role in tumor invasion is unclear. A growing number of studies have demonstrated that lactic acid regulates the degradation of collagen Ⅳ, collagen Ⅶ, and glycoprotein; the synthesis of collagen Ⅰ; and multiple signaling pathways, including TGF-β/Smad, Wnt/β-catenin, IL-6/STAT3, and HGF/MET, which are associated with basement membrane (BM) remodeling and epithelial-mesenchymal transition (EMT), two hallmarks of the tumor invasive process. In the present review, we summarize BM remodeling and EMT in tumor invasion, discuss the emerging roles and molecular mechanisms of lactic acid in these processes, and provide insights for further research.