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Cell of Origin of Small Cell Lung Cancer: Inactivation of Trp53 and Rb1 in Distinct Cell Types of Adult Mouse Lung
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Small cell lung cancer (SCLC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we assessed the effect of Trp53 and Rb1 inactivation in distinct cell types in the adult lung using adenoviral vectors that target Cre recombinase to Clara, neuroendocrine (NE), and alveolar type 2 (SPC-expressing) cells. Using these cell type-restricted Adeno-Cre viruses, we show that loss of Trp53 and Rb1 can efficiently transform NE and SPC-expressing cells leading to SCLC, albeit SPC-expressing cells at a lesser efficiency. In contrast, Clara cells were largely resistant to transformation. The results indicate that although NE cells serve as the predominant cell of origin of SCLC a subset of SPC-expressing cells are also endowed with this ability.
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“In particular, there is preclinical evidence that type II alveolar cells have the potential to differentiate into SCLC after the targeted disruption of Tp53 and Rb1.35”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [35]
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Huisman, D. H., Chatterjee, D., Ireland, A. S., Skupa, S. A., Girard, L., Fisher, K. W., Kareta, M. S., Minna, J. D., Oliver, T. G., & Lewis, R. E. (2025) · Qeios · doi:10.32388/ccylg3
Gao, Y., Yao, B., He, S., Zhang, G., Zhang, X., Qi, R., Ma, X., Li, X., Chen, X., Zheng, H., et al. (2025) · Medicine · doi:10.1097/md.0000000000041820
Cells of Origin and Tumor Heterogeneity in Lung Cancer Guide Personalized Therapeutic StrategiesPreprint
Liang, J., Liu, Y., Teng, X., Zhao, Y. Q., Zeng, J., Ning, W., Xu, Z., Zhao, J., Yao, M., Tang, J., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-7441718/v1
Metadata
- Authors
- Sutherland, K. D., Proost, N., Brouns, I., Adriaensen, D., Song, J.-Y., & Berns, A.
- Affiliations
- The Netherlands Cancer Institute (NL)
- University of Antwerp (BE)
- Corresponding author
- Berns, Anton
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 19
- Issue
- 6
- Pages
- 754-764
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1972570571
- Cited by
- 534
- References
- 48
- Citations by year
- 2026: 22 · 2025: 54 · 2024: 41 · 2023: 48 · 2022: 33 · 2021: 50 · 2020: 40 · 2019: 28 · 2018: 37 · 2017: 33 · 2016: 31 · 2015: 33 · 2014: 20 · 2013: 27 · 2012: 21
- FWCI
- 13.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 813 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council (516781)
- Fonds De La Recherche Scientifique - FNRS
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- small cell lung cancer, cell of origin, RB1 inactivation, Clara cells, neuroendocrine cells, alveolar type II cells
- MeSH terms
- Adenoviridae, Animals, Cell Transformation, Neoplastic, Lung, Lung Neoplasms, Tumor Suppressor Protein p53, Retinoblastoma Protein, Integrases, Mice, Neuroendocrine Cells, Small Cell Lung Carcinoma
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