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• W2406860897 abstract "Background & AimsPancreatitis is the most important risk factor for pancreatic ductal adenocarcinoma (PDAC). Pancreatitis predisposes to PDAC because it induces a process of acinar cell reprogramming known as acinar-to-ductal metaplasia (ADM)—a precursor of pancreatic intraepithelial neoplasia lesions that can progress to PDAC. Mutations in KRAS are found at the earliest stages of pancreatic tumorigenesis, and it appears to be a gatekeeper to cancer progression. We investigated how mutations in KRAS cooperate with pancreatitis to promote pancreatic cancer progression in mice.MethodsWe generated mice carrying conditional alleles of Yap1 and Taz and disrupted Yap1 and Taz using a Cre-lox recombination strategy in adult mouse pancreatic acinar cells (Yap1fl/fl;Tazfl/fl;Ela1-CreERT2). We crossed these mice with LSL-KrasG12D mice, which express a constitutively active form of KRAS after Cre recombination. Pancreatic tumor initiation and progression were analyzed after chemically induced pancreatitis. We analyzed pancreatic tissues from patients with pancreatitis or PDAC by immunohistochemistry.ResultsOncogenic activation of KRAS in normal, untransformed acinar cells in the pancreatic tissues of mice resulted in increased levels of pancreatitis-induced ADM. Expression of the constitutive active form of KRAS in this system led to activation of the transcriptional regulators YAP1 and TAZ; their function was required for pancreatitis-induced ADM in mice. The JAK–STAT3 pathway was a downstream effector of KRAS signaling via YAP1 and TAZ. YAP1 and TAZ directly mediated transcriptional activation of several genes in the JAK–STAT3 signaling pathway; this could be a mechanism by which acinar cells that express activated KRAS become susceptible to inflammation.ConclusionsWe identified a mechanism by which oncogenic KRAS facilitates ADM and thereby generates the cells that initiate neoplastic progression. This process involves activation of YAP1 and TAZ in acinar cells, which up-regulate JAK–STAT3 signaling to promote development of PDAC in mice. Pancreatitis is the most important risk factor for pancreatic ductal adenocarcinoma (PDAC). Pancreatitis predisposes to PDAC because it induces a process of acinar cell reprogramming known as acinar-to-ductal metaplasia (ADM)—a precursor of pancreatic intraepithelial neoplasia lesions that can progress to PDAC. Mutations in KRAS are found at the earliest stages of pancreatic tumorigenesis, and it appears to be a gatekeeper to cancer progression. We investigated how mutations in KRAS cooperate with pancreatitis to promote pancreatic cancer progression in mice. We generated mice carrying conditional alleles of Yap1 and Taz and disrupted Yap1 and Taz using a Cre-lox recombination strategy in adult mouse pancreatic acinar cells (Yap1fl/fl;Tazfl/fl;Ela1-CreERT2). We crossed these mice with LSL-KrasG12D mice, which express a constitutively active form of KRAS after Cre recombination. Pancreatic tumor initiation and progression were analyzed after chemically induced pancreatitis. We analyzed pancreatic tissues from patients with pancreatitis or PDAC by immunohistochemistry. Oncogenic activation of KRAS in normal, untransformed acinar cells in the pancreatic tissues of mice resulted in increased levels of pancreatitis-induced ADM. Expression of the constitutive active form of KRAS in this system led to activation of the transcriptional regulators YAP1 and TAZ; their function was required for pancreatitis-induced ADM in mice. The JAK–STAT3 pathway was a downstream effector of KRAS signaling via YAP1 and TAZ. YAP1 and TAZ directly mediated transcriptional activation of several genes in the JAK–STAT3 signaling pathway; this could be a mechanism by which acinar cells that express activated KRAS become susceptible to inflammation. We identified a mechanism by which oncogenic KRAS facilitates ADM and thereby generates the cells that initiate neoplastic progression. This process involves activation of YAP1 and TAZ in acinar cells, which up-regulate JAK–STAT3 signaling to promote development of PDAC in mice." @default.
• W2406860897 created "2016-06-24" @default.
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• W2406860897 date "2016-09-01" @default.
• W2406860897 modified "2023-10-18" @default.
• W2406860897 title "YAP1 and TAZ Control Pancreatic Cancer Initiation in Mice by Direct Up-regulation of JAK–STAT3 Signaling" @default.
• W2406860897 cites W1964064067 @default.
• W2406860897 cites W1969104713 @default.
• W2406860897 cites W1974286326 @default.
• W2406860897 cites W1982781304 @default.
• W2406860897 cites W1987220381 @default.
• W2406860897 cites W1992995822 @default.
• W2406860897 cites W2008996257 @default.
• W2406860897 cites W2021766591 @default.
• W2406860897 cites W2025970479 @default.
• W2406860897 cites W2027150010 @default.
• W2406860897 cites W2028593002 @default.
• W2406860897 cites W2031505107 @default.
• W2406860897 cites W2033589713 @default.
• W2406860897 cites W2040430549 @default.
• W2406860897 cites W2041255962 @default.
• W2406860897 cites W2043497705 @default.
• W2406860897 cites W2048621454 @default.
• W2406860897 cites W2048669411 @default.
• W2406860897 cites W2054024439 @default.
• W2406860897 cites W2056646351 @default.
• W2406860897 cites W2066135299 @default.
• W2406860897 cites W2066707761 @default.
• W2406860897 cites W2072304718 @default.
• W2406860897 cites W2079015343 @default.
• W2406860897 cites W2081681778 @default.
• W2406860897 cites W2088693506 @default.
• W2406860897 cites W2089784089 @default.
• W2406860897 cites W2091054780 @default.
• W2406860897 cites W2091694499 @default.
• W2406860897 cites W2099709490 @default.
• W2406860897 cites W2101151845 @default.
• W2406860897 cites W2130112621 @default.
• W2406860897 cites W2130410032 @default.
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• W2406860897 cites W2133591242 @default.
• W2406860897 cites W2135726634 @default.
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• W2406860897 cites W2153517086 @default.
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• W2406860897 cites W2157912474 @default.
• W2406860897 cites W2158217645 @default.
• W2406860897 cites W2161884651 @default.
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• W2406860897 doi "https://doi.org/10.1053/j.gastro.2016.05.006" @default.
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