Fiche publication
Date publication
mai 2024
Journal
American journal of physiology. Gastrointestinal and liver physiology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Pravoverov K, Fatima I, Barman S, Jühling F, Primeaux M, Baumert T, Singh AB, Dhawan P
Lien Pubmed
Résumé
Microtubule-associated serine-threonine kinase-like (MASTL) has recently been identified as a oncogenic kinase given its overexpression in numerous cancers. Our group has shown that MASTL expression is upregulated in mouse models of sporadic CRC and colitis associated cancer (CAC). CAC is one of the most severe complications of chronic IBD, but a limited understanding of the mechanisms governing the switch from normal healing to neoplasia in IBD underscores the need for increased research in this area. However, MASTL expression in IBD patients and its molecular regulation in IBD and CAC have not been studied. This study reveals that MASTL is upregulated by the cytokine interleukin (IL)-22, which promotes proliferation and has important functions in colitis recovery; however, IL-22 can also promote tumorigenesis when chronically elevated. Upon reviewing the publicly available data, we found significantly elevated MASTL and IL-22 levels in the biopsies from late-stage ulcerative colitis patients compared to controls, and that MASTL upregulation was associated with high IL-22 expression. Our subsequent in vitro studies found that IL-22 increases MASTL expression in intestinal epithelial cell lines, facilitating IL-22- mediated cell proliferation and downstream survival signaling. Inhibition of AKT activation abrogated IL-22-induced MASTL upregulation. We further found an increased association of carbonic anhydrase IX (CAIX) with MASTL in IL-22-treated cells, which stabilized MASTL expression. Inhibition of CAIX prevented IL-22-induced MASTL expression and cell survival. Overall, we show that IL-22/AKT signaling increases MASTL expression to promote cell survival and proliferation. Further, CAIX stabilizes MASTL by associating with it in response to IL-22 stimulation.
Mots clés
carbonic anhydrase 9 (CA9 or CAIX), colitis, colitis-associated cancer (CAC), interleukin 22 (IL-22), microtubule-associated serine-threonine kinase-like (MASTL)
Référence
Am J Physiol Gastrointest Liver Physiol. 2024 05 21;:
