Abstract
Aim
SLC16A8, a lactate efflux transporter, is upregulated in various cancers, but its effect on tumor microenvironments remains understudied. This research explores its role in colorectal cancer and the impact on the associated microenvironment consisting of vascular endothelial cells.
Methods
Hypoxic conditions prompted examination of SLC16A8 expression, glycolysis, lactate efflux, and Warburg effect correlations in colorectal cancer cell lines. Co-culture with HUVEC allowed for EndMT characterization, revealing lactate efflux's influence. Knockdown of SLC16A8 in colorectal cancer cells enabled relevant phenotype tests and tumorigenesis experiments, investigating tumor growth, blood vessel distribution, and signaling pathway alterations.
Results
Under hypoxic conditions, SLC16A8 upregulation not only promoted anaerobic glycolysis, LDHA, and PKM2 expression in colorectal cancer cells but also suggested Warburg effect involvement. Co-culturing with HUVEC triggered an increase in EndMT characteristics in endothelial cells. Knocking down SLC16A8 reversed these phenotypes in both cell types. In vivo, SLC16A8 inhibition led to reduced tumor growth, decreased angiogenesis, and enhanced apoptosis signals. SLC16A8 plays a pivotal role in promoting tumor angiogenesis and fostering a favorable environment for colorectal cancer development.
Conclusions
The findings emphasize the importance of addressing lactate efflux in cancer therapy and warrant further investigation into SLC16A8 as a potential therapeutic target.