The DOI matches its Crossref record; 62 of the 64 references it cites were found in a registry or an index.
K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling
Open accessAbstract
K-Ras and H-Ras share identical effectors and have similar properties; however, the high degree of tumor-type specificity associated with K-Ras and H-Ras mutations suggests that they have unique roles in oncogenesis. Here, we report that oncogenic K-Ras, but not H-Ras, suppresses non-canonical Wnt/Ca(2+) signaling, an effect that contributes strongly to its tumorigenic properties. K-Ras does this by binding to calmodulin and so reducing CaMKii activity and expression of Fzd8. Restoring Fzd8 in K-Ras mutant pancreatic cells suppresses malignancy, whereas depletion of Fzd8 in H-Ras(V12)-transformed cells enhances their tumor initiating capacity. Interrupting K-Ras-calmodulin binding using genetic means or by treatment with an orally active protein kinase C (PKC)-activator, prostratin, represses tumorigenesis in K-Ras mutant pancreatic cancer cells. These findings provide an alternative way to selectively target this "undruggable" protein.
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“and stemness properties in tumor cells through its ability to suppress non-canonical Wnt signaling (15).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [15]
Citations
Cites
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“K-Ras mutations occur at high frequency in pancreatic and colorectal cancers and in lung adenocarcinomas, while N-Ras and H-Ras mutations are far less common (Prior et al., 2012).”
BackgroundSubtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy
Collisson, E. A., Sadanandam, A., Olson, P., Gibb, W. J., Truitt, M., Gu, S., Cooc, J., Weinkle, J., Kim, G. E., Jakkula, L., et al. (2011) · Nature Medicine · doi:10.1038/nm.2344 · Cited by 1,967
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
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RAS oncogenes: the first 30 years
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“Furthermore, K-Ras deficiency results in embryonic lethality, whereas N- and H-Ras knockout mice develop normally (Johnson et al., 1997; Koera et al., 1997; Malumbres and Barbacid, 2003).”
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2 of the 64 references couldn’t be matched to a known paper.
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RAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943
Self-citationDirect small-molecule inhibitors of KRAS: from structural insights to mechanism-based design
Ostrem, J. M. L., & Shokat, K. M. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.139 · Cited by 641
The calcium–cancer signalling nexus
Monteith, G. R., Prevarskaya, N. B., & Roberts‐Thomson, S. J. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.18 · Cited by 649
Genetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527
Katoh, M. (2017) · International Journal of Oncology · doi:10.3892/ijo.2017.4129 · Cited by 478
Metadata
- Authors
- Wang, M.-T., Holderfield, M., Galeas, J., Delrosario, R., To, M. D., Balmain, A., & McCormick, F.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- McCormick, Frank
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 163
- Issue
- 5
- Pages
- 1237-1251
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2175955272
- Cited by
- 196
- References
- 64
- Citations by year
- 2026: 13 · 2025: 4 · 2024: 6 · 2023: 14 · 2022: 18 · 2021: 19 · 2020: 23 · 2019: 17 · 2018: 21 · 2017: 30 · 2016: 27 · 2015: 1
- FWCI
- 11.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lustgarten Foundation
- Daiichi-Sankyo
- National Institutes of Health
- Daiichi Sankyo Europe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- KRAS, H-Ras, calmodulin, CaMKII, FZD8, pancreatic cancer, tumorigenicity, prostratin, protein kinase C, tumor initiation
- MeSH terms
- Amino Acid Sequence, Animals, Calmodulin, Disease Models, Animal, Female, Humans, Molecular Sequence Data, Pancreatic Neoplasms, Papilloma, Phorbol Esters, Phosphorylation, Protein Binding, Genes, ras, Receptors, Cell Surface, Proto-Oncogene Proteins p21(ras), Animals, Genetically Modified, Cell Line, Tumor, Mice, Wnt Signaling Pathway
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