Globular adiponectin and its downstream target genes are up-regulated locally in human colorectal tumors: ex vivo and in vitro studies.

OBJECTIVE

Low plasma adiponectin levels are linked to obesity, insulin resistance, and the risk of several types of malignancy. Despite the decline in circulating adiponectin concentrations, the increase in the expression of adiponectin receptors AdipoR1 and AdipoR2 is greater in cancerous than in normal colonic tissue. The purpose of this study was to obtain new information regarding local adiponectin signaling in the pathogenesis of colorectal cancer (CRC).

METHODS

We characterized the expressions of adiponectin and several of its downstream targets in paired samples of tumor tissue and adjacent noncancerous mucosa in 60 surgical patients with colorectal adenocarcinomas.

RESULTS

Adiponectin was expressed in both colorectal tumors and the adjacent mucosa. The expressions of adiponectin mRNA and its globular protein variant (gAd), adiponectin receptor type 1 and 5' AMP-activated protein kinase (AMPK) mRNA were significantly higher in colorectal tumors than in the adjacent mucosa. This finding was accompanied by increased mRNA expression of genes encoding proteins involved in fatty-acid trafficking and oxidation. The potential interference between adiponectin stimulation and AMPK activation through AMPK1 was examined in an in vitro model with the aid of silencing-RNA experiments. Furthermore, AMPK mRNA expression on tumors was positively correlated with a more advanced tumor stage in the patients.

CONCLUSION

We propose that the globular adiponectin-AMPK pathway functions in an autocrine manner in colorectal tumors, explaining some of the beneficial changes in cellular oxidative capacity in tumors in favor of tumorigenesis.