Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma.

BACKGROUND/AIM: Ethylmalonic encephalopathy 1 protein (ETHE1) plays an important role in sulfide catabolism and polysulfide formation. As sulfides and polysulfides have recently been identified as playing important roles in cancer, we hypothesized that ETHE1 expression would be increased in colon cancer. MATERIALS AND METHODS: We used tissue microarray analysis to compare ETHE1 expression in benign colonic epithelium compared to colonic adenocarcinoma. In total, 26 benign colonic epithelial samples were compared to 122 cases of colonic adenocarcinomas. RESULTS: Compared to benign colonic epithelium, ETHE1 expression was significantly increased (~two-fold) in colonic adenocarcinoma. Additionally, this expression increased with increasing colon cancer tumor grades. CONCLUSION: ETHE1 expression is increased in colon cancer compared to benign colonic epithelium. These data, combined with previous studies, suggest that ETHE1 may contribute to colon carcinogenesis by promoting tumor cell bioenergetics and polysulfide formation.

Molecular Functions of Hydrogen Sulfide in Cancer.

Hydrogen sulfide (H2S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H2S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H2S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia-mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H2S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H2S in cancer, with an emphasis on the molecular mechanisms by which H2S promotes cancer development, progression, dedifferentiation, and metastasis.