Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma
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Without the transcription regulator YAP, KRAS-mutant pancreatic neoplasia cannot progress into invasive cancer.
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YAP1 signaling is essential for initiation of KRAS-driven PDAC.
“However, previous studies have demonstrated that YAP1 signaling is essential for the initiation of KRAS-driven PDAC.43”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [43]
The Discussion calls acinar-to-ductal metaplasia (ADM) the initiating step in PDAC development and says Yap is dispensable for it. The Results likewise report that Yap deletion did not affect KRAS-induced ADM. The paper instead finds YAP necessary for subsequent progression to late-stage PanINs and PDAC. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredKRAS mutations activate YAP-TAZ and JAK-STAT pathways, leading to release of immunosuppressive cytokines such as CSF-1, IL-4, IL-6.
“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 [65]
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- Authors
- Zhang, W., Nandakumar, N., Shi, Y., Manzano, M., Smith, A., Graham, G., Gupta, S., Vietsch, E. E., Laughlin, S. Z., Wadhwa, M., Chetram, M., Joshi, M., Wang, F., Kallakury, B., Toretsky, J., Wellstein, A., & Yi, C.
- Affiliations
- Georgetown University Medical Center (US)
- Corresponding author
- Yi, Chunling
- ORCID
- Venue
- Science Signaling
- Published
- 2014-05-06
- Volume
- 7
- Issue
- 324
- Pages
- ra42-ra42
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC4175524
- OpenAlex
- W2091694499
- Cited by
- 360
- References
- 126
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 18 · 2023: 25 · 2022: 31 · 2021: 42 · 2020: 30 · 2019: 40 · 2018: 32 · 2017: 29 · 2016: 42 · 2015: 34 · 2014: 9
- FWCI
- 19.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA133662, R33CA177466, CA051008, R01CA138212, CA 71508, R01CA071508, P30CA051008, T32CA009686)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- pancreatic ductal adenocarcinoma, KRAS mutation, YAP, Hippo signaling pathway, acinar-to-ductal metaplasia, Trp53, MAPK signaling, tumor microenvironment, secreted factors, cell proliferation, therapeutic target
- MeSH terms
- YAP-Signaling Proteins, Adenocarcinoma, Animals, Humans, Mutation, Pancreatic Ducts, Phosphoproteins, Genes, ras, RNA, Messenger, Transcription Factors, Genes, p53, Disease Progression, Carcinoma, Pancreatic Ductal, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice
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