Keep a watchful eye on methionine adenosyltransferases, novel therapeutic opportunities for hepatobiliary and pancreatic tumours

Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188793. doi: 10.1016/j.bbcan.2022.188793. Epub 2022 Sep 9.

Abstract

Methionine adenosyltransferases (MATs) synthesize S-adenosylmethionine (SAM) from methionine, which provides methyl groups for DNA, RNA, protein, and lipid methylation. MATs play a critical role in cellular processes, including growth, proliferation, and differentiation, and have been implicated in tumour development and progression. The expression of MATs is altered in hepatobiliary and pancreatic (HBP) cancers, which serves as a rare biomarker for early diagnosis and prognosis prediction of HBP cancers. Independent of SAM depletion in cells, MATs are often dysregulated at the transcriptional, post-transcriptional, and post-translational levels. Dysregulation of MATs is involved in carcinogenesis, chemotherapy resistance, T cell exhaustion, activation of tumour-associated macrophages, cancer stemness, and activation of tumourigenic pathways. Targeting MATs both directly and indirectly is a potential therapeutic strategy. This review summarizes the dysregulations of MATs, their proposed mechanism, diagnostic and prognostic roles, and potential therapeutic effects in context of HBP cancers.

Keywords: Hepatobiliary cancer; Immunotherapy; Methionine adenosyltransferase; Methionine metabolism; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gastrointestinal Neoplasms*
  • Humans
  • Lipids
  • Methionine
  • Methionine Adenosyltransferase / genetics
  • Methionine Adenosyltransferase / metabolism
  • Pancreatic Neoplasms* / drug therapy
  • RNA
  • S-Adenosylmethionine / metabolism
  • S-Adenosylmethionine / therapeutic use

Substances

  • Lipids
  • Methionine
  • Methionine Adenosyltransferase
  • RNA
  • S-Adenosylmethionine