biostudies-literatureGarg BStand Up To Cancer (SU2C)Pancreatic Cancer Canada Foundation (PCCF)Foundation for the National Institutes of Health (FNIH)CCSGthe Terry Fox Research InstitutePrincess Margaret Cancer Foundation (PMCF)Ontario Institute for Cancer Research (OICR)Lustgarten Foundation (Lustgarten)Research for a cure of Pancreactic cancerPancreatic Cancer Action Network (PCAN)the Canadian Cancer Society Research InstituteNCI NIH HHSSyros Pharmaceuticles, Inc. Cambridge MA1049-1063https://www.ebi.ac.uk/biostudies/studies/S-EPMC11907191biostudies-literatureUnknown85(6)Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid cancers; thus, identifying more effective therapies is a major unmet need. In this study, we characterized the super-enhancer (SE) landscape of human PDAC to identify drivers of the disease that might be targetable. This analysis revealed MICAL2 as an SE-associated gene in human PDAC, which encodes the flavin monooxygenase enzyme that induces actin depolymerization and indirectly promotes serum response factor transcription by modulating the availability of serum response factor coactivators such as myocardin-related transcription factors (MRTF-A and MRTF-B). MICAL2 was overexpressed in PDAC, and high-MICAL2 expression correlated with poor patient prognosis. Transcriptional analysis revealed that MICAL2 upregulates Cancer researchMICAL2 Promotes Pancreatic Cancer Growth and Metastasis.PMC11907191T32 CA121938U54 CA285115U54 CA285117F31 CA257344P01 CA265762CA 273973U01 CA274295P30 CA051008U24 CA220341T32 CA067754P30CA23100R21 CA273973P30 CA023100R01 CA207189Rajbhandari NSheik Pran Babu DSood DEsparza ELambies GTamayo PD'Ippolito ABrodt PGallinger SMose ESCommisso CTiriac HJaquish DPatel JPanneerpandian PLowy AMJang GHSharma SMartsinkovskiy AGarg BAustgen KCourelli ASWenzel ATGoodfellow EGulay KCMJohnston BJaque KAggarwal NOrlando DAMesirov JPKhan SfalseMICAL2 Promotes Pancreatic Cancer Growth and Metastasis.Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid cancers; thus, identifying more effective therapies is a major unmet need. In this study, we characterized the super-enhancer (SE) landscape of human PDAC to identify drivers of the disease that might be targetable. This analysis revealed MICAL2 as an SE-associated gene in human PDAC, which encodes the flavin monooxygenase enzyme that induces actin depolymerization and indirectly promotes serum response factor transcription by modulating the availability of serum response factor coactivators such as myocardin-related transcription factors (MRTF-A and MRTF-B). MICAL2 was overexpressed in PDAC, and high-MICAL2 expression correlated with poor patient prognosis. Transcriptional analysis revealed that MICAL2 upregulates 2025-01-01T00:00:00Z2025 Mar2026-06-02T07:17:19.612Z2025-04-05T12:39:07.709ZS-EPMC119071913974535210.1158/0008-5472.CAN-24-0744