Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 243, Issue 2, Pages 107-117Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370217740860
Keywords
Chemoprevention; cholangiocarcinoma; colon cancer; hepatocellular carcinoma; methionine adenosyltransferase; S-adenoylmethionine
Categories
Funding
- NIH [R01AT001576, R01 CA172086, R01DK107288, R01DK092407]
- Plan Nacional of I+D SAF [2014-52097R]
- Severo Ochoa Excellence Accreditation [SEV-2016-0644]
Ask authors/readers for more resources
Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes-MAT1A, MAT2A, and MAT2B-with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues. Increasing evidence suggests that methionine adenosyltransferases play significant roles in the development of cancers. Liver cancers, namely hepatocellular carcinoma and cholangiocarcinoma, involve dysregulation of all three methionine adenosyltransferase genes. MAT1A reduction is associated with increased oxidative stress, progenitor cell expansion, genomic instability, and other mechanisms implicated in tumorigenesis. MAT2A/MAT2B induction confers growth and survival advantage to cancerous cells, enhancing tumor migration. Highlighted examples from colon, gastric, breast, pancreas and prostate cancer studies further underscore methionine adenosyltransferase genes' role beyond the liver in cancer development. In this subset of extra-hepatic cancers, MAT2A and MAT2B are induced via different regulatory mechanisms. Understanding the role of methionine adenosyltransferase genes in tumorigenesis helps identify attributes of these genes that may serve as valuable targets for therapy. While S-adenosylmethionine, and its metabolite, methylthioadenosine, have been largely explored as therapeutic interventions, targets aimed at regulation of MAT gene expression and methionine adenosyltransferase protein-protein interactions are now surfacing as potential effective strategies for treatment and chemoprevention of cancers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available