The DOI matches its Crossref record; 49 of the 51 references it cites were found in a registry or an index.
STAT3 Plays a Critical Role in KRAS -Induced Pancreatic Tumorigenesis
Open accessPublished version of a preprint
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 a JAK2 inhibitor that blocks STAT3 function revealed a more than 30-fold range in sensitivity in PDAC, and showed a close correlation of sensitivity with levels of tyrosine-phosphorylated STAT3 and of the gp130 receptor, an upstream signaling component. Correspondingly, upregulation of the IL6/LIF-gp130 pathway accounted for the strong STAT3 activation in PDAC subsets. To define functions of STAT3 in vivo, we developed mouse models that test the impact of conditional inactivation of STAT3 in KRAS-driven PDAC. We showed that STAT3 is required for the development of the earliest premalignant pancreatic lesions, acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Moreover, acute STAT3 inactivation blocked PDAC initiation in a second in vivo model. Our results show that STAT3 has critical roles throughout the course of PDAC pathogenesis, supporting the development of therapeutic approaches targeting this pathway. Moreover, our work suggests that gp130 and phospho-STAT3 expression may be effective biomarkers for predicting response to JAK2 inhibitors. Cancer Res; 71(14); 5020–9. ©2011 AACR.
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“KRAS mutations activate Yes-associated protein-tafazzin (YAP-TAZ) and Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathways, leading to release of immunosuppressive cytokines such as CSF-1, IL-4, IL-6.”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [66]
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Citations
Cites
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471
Zhong, Z., Wen, Z., & Darnell, J. E. (1994) · Science · doi:10.1126/science.8140422 · Cited by 2,070 · cited 1×
“Classically, STAT tyrosine phosphorylation is mediated by the Janus-activated kinase (JAK) family of tyrosine kinases, which themselves are activated by cytokine and growth factor receptors (10, 11).”
Genetics and biology of pancreatic ductal adenocarcinomaPreprint
Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N. M., & DePinho, R. A. (2006) · Genes & Development · doi:10.1101/gad.1415606 · Cited by 1,611
Self-citationGu, G., Dubauskaite, J., & Melton, D. A. (2002) · Development · doi:10.1242/dev.129.10.2447 · Cited by 1,518
Iliopoulos, D., Hirsch, H. A., & Struhl, K. (2009) · Cell · doi:10.1016/j.cell.2009.10.014 · Cited by 1,374
Interleukin-6 family of cytokines and gp130.
Kishimoto, T., Akira, S., Narazaki, M., & Taga, T. (1995) · Blood · doi:10.1182/blood.v86.4.1243.bloodjournal8641243 · Cited by 1,362 · cited 2×
“STAT3 is activated by numerous growth factor and cytokine signaling pathways as well as by oncogenic RAS (7, 34, 43).”
The transcriptional network for mesenchymal transformation of brain tumours
Carro, M. S., Lim, W. K., Alvarez, M. J., Bollo, R. J., Zhao, X., Snyder, E. Y., Sulman, E. P., Anne, S. L., Doetsch, F. K., Colman, H., et al. (2009) · Nature · doi:10.1038/nature08712 · Cited by 1,268
The role of STATs in transcriptional control and their impact on cellular function
Bromberg, J., & Darnell, J. E. (2000) · Oncogene · doi:10.1038/sj.onc.1203476 · Cited by 1,201 · cited 1×
“Subsequent studies identified key functions for STAT proteins in the maintenance of self-renewal of embryonic stem cells and in the activation of proliferative, antiapoptotic, and inflammatory pathways to initiate and maintain growth of a number of tumor types (7, 13, 14).”
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Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression
Rielland, M., Cantor, D. J., Graveline, R., Hajdu, C., Mara, L., de Diego Diaz, B., Miller, G., & David, G. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72619 · Cited by 76
“This notion is particularly relevant to PDAC, as its progression is intimately linked to inflammation (1, 22–26).”
Circumventing senescence is associated with stem cell properties and metformin sensitivity
Deschênes‐Simard, X., Parisotto, M., Rowell, M., Le Calvé, B., Igelmann, S., Moineau‐Vallée, K., Saint‐Germain, E., Kalegari, P., Bourdeau, V., Kottakis, F., et al. (2019) · Aging Cell · doi:10.1111/acel.12889 · Cited by 45
“1,497, 1,498, and 1,499 pancreatic ductal cell lines were isolated from 9‐week‐old Pdx1‐Cre;LSL‐ Kras mice as reported previously (Corcoran et al., 2011).”
MethodSelf-citationGu, M., Gao, Y., & Chang, P. (2021) · Cancers · doi:10.3390/cancers13102429 · Cited by 35
“In the presence of KRASG12D mutation, Stat3 was revealed to be required for the development of ADM and PanIN during pancreatic carcinogenesis in mice [41].”
BackgroundPolymer Thin Film-Induced Tumor Spheroids Acquire Cancer Stem Cell-like Properties
Choi, M., Yu, S. J., Choi, Y., Lee, H. R., Lee, E., Lee, E., Lee, Y., Song, J., Son, J. G., Lee, T. G., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0927 · Cited by 32
Blaszczak, W., White, B., Monterisi, S., & Swietach, P. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113612 · Cited by 9
Metadata
- Authors
- Corcoran, R. B., Contino, G., Deshpande, V., Tzatsos, A., Conrad, C., Benes, C. H., Levy, D. E., Settleman, J., Engelman, J. A., & Bardeesy, N.
- Affiliations
- Harvard University (US)
- Corresponding author
- Bardeesy, Nabeel
- ORCID
- Venue
- Cancer Research
- Published
- 2011-07-14
- Volume
- 71
- Issue
- 14
- Pages
- 5020-5029
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3693754
- OpenAlex
- W2133591242
- Cited by
- 413
- References
- 51
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 18 · 2023: 32 · 2022: 28 · 2021: 39 · 2020: 30 · 2019: 32 · 2018: 24 · 2017: 35 · 2016: 35 · 2015: 30 · 2014: 32 · 2013: 28 · 2012: 18
- FWCI
- 12.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Fondazione Umberto Veronesi
- National Institutes of Health
- National Cancer Institute (P50CA127003, R01CA133557, P01CA117969, T32CA071345)
- National Institute of Allergy and Infectious Diseases (R0AI28900)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- STAT3, pancreatic ductal adenocarcinoma, JAK2 inhibitors, acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia, premalignant pancreatic lesions, predictive biomarkers
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Humans, Mice, Transgenic, Pancreatic Neoplasms, Phosphorylation, Precancerous Conditions, Genes, ras, Transcriptional Activation, Mice, SCID, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, STAT3 Transcription Factor, Mice
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