Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis
Open accessAbstract
Significance Oncogenic KRAS underlies 30–90% of lung, colon, and pancreatic cancers, but despite more than 30 y of research, clinical inhibitors of KRAS—and potential resistance mechanisms—remain elusive. Using CRISPR-mediated genome editing of oncogenic Kras , we show that some lung cancer cells can survive Kras knockout, indicating the existence of mechanisms that allow tumors to escape Kras oncogene addiction. We identify genes highly expressed in Kras knockout cells, including the Fas receptor gene. Antibodies that activate Fas receptor selectively induced apoptosis in Kras-independent lung cancer cells, suggesting a potential strategy for combinatorial therapies against Kras-driven tumors. These findings have direct translational implications for the treatment of lung cancer and other KRAS mutant cancer types.
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Some KRAS-mutant cancer cells, including lung and pancreatic cancer cells, can survive in the absence of the KRAS oncogene.
“some KRAS-mutant cancer cells, including lung (20) and pancreatic cancer cells (21, 22), can survive in the absence of the KRAS oncogene.”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [20]
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- Authors
- Mou, H., Moore, J., Malonia, S. K., Li, Y., Ozata, D. M., Hough, S., Song, C.-Q., Smith, J. L., Fischer, A., Weng, Z., Green, M. R., & Xue, W.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Tongji University (CN)
- RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605;
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-03-20
- Volume
- 114
- Issue
- 14
- Pages
- 3648-3653
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5389295
- OpenAlex
- W2598000851
- Cited by
- 46
- References
- 47
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 12 · 2018: 4 · 2017: 4
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- HHS | NIH | National Cancer Institute (R00 CA169512)
- HHS | NIH | National Heart, Lung, and Blood Institute (DP2 HL137167)
- American Cancer Society (129056-RSG-16-093)
- Lung Cancer Research Foundation (2015-Xue)
- China Scholarship Council (201506260151)
- Howard Hughes Medical Institute (068101)
- 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 › Cell death mechanisms and regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- oncogenic KRAS, lung cancer, Fas, apoptosis, oncogene addiction, CRISPR gene editing, combination therapy, KRAS-mutant cancer
- MeSH terms
- Animals, Antibodies, Carcinoma, Non-Small-Cell Lung, Cell Survival, Humans, Lung Neoplasms, Mutation, Neoplasm Transplantation, Promoter Regions, Genetic, Up-Regulation, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins p21(ras), fas Receptor, Gene Expression Profiling, Epigenesis, Genetic, Cell Line, Tumor, Mice, Gene Knockout Techniques
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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