2011
DOI: 10.1158/0008-5472.can-11-0908
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STAT3 Plays a Critical Role in KRAS-Induced Pancreatic Tumorigenesis

Abstract: The STAT3 transcription factor is an important regulator of stem cell self-renewal, cancer cell survival, and inflammation. In the pancreas, STAT3 is dispensable for normal development whereas the majority of pancreatic ductal adenocarcinomas (PDAC) show constitutive activation of STAT3, suggesting its potential as a therapeutic target in this cancer. Here, we sought to define the mechanisms of STAT3 activation and its functional importance in PDAC pathogenesis. Large-scale screening of cancer cell lines with … Show more

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Cited by 362 publications
(353 citation statements)
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“…4A). Signaling pathways including PI3K/S6, ERK, STAT3, and β-catenin have been reported to be activated in PDAC (3,30,31). As expected, these pathways were prominently up-regulated in the PKC pancreata (Fig.…”
Section: Suppression Of Proliferation and Oncogenic Signaling In Pkc7supporting
confidence: 72%
“…4A). Signaling pathways including PI3K/S6, ERK, STAT3, and β-catenin have been reported to be activated in PDAC (3,30,31). As expected, these pathways were prominently up-regulated in the PKC pancreata (Fig.…”
Section: Suppression Of Proliferation and Oncogenic Signaling In Pkc7supporting
confidence: 72%
“…These are two new and important findings because previous studies have suggested that JAK1 and JAK2 are capable of activating STAT3 in response to inflammatory cytokines in diverse cell culture models (reviewed by Kisseleva et al [20]). Although it was recognized nearly 2 decades ago that JAK1 plays a role in IL-6 signaling (21,45,46), more recent work has singled out JAK2 as the master regulator for STAT3 activation in breast cancer and other malignancies (47)(48)(49). This paradigm is likely the result of the fact that pharmacological agents labeled "JAK2 inhibitors" were being utilized in most of the recently published experiments.…”
Section: Discussionmentioning
confidence: 99%
“…Thus, these new findings unveil a novel epithelial − stromal crosstalk with profound implications for tumour composition and progression. In light of this study and previous results that highlighted the role of STAT3 in PDAC development, 11 the identification of any pathways that stimulate STAT3 signalling in PDAC may reveal additional therapeutic opportunities.…”
mentioning
confidence: 63%