The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer
Open accessAbstract
Small cell lung cancer (SCLC) is widely considered to be a tumor of pulmonary neuroendocrine cells; however, a variant form of this disease has been described that lacks neuroendocrine features. Here, we applied domain-focused CRISPR screening to human cancer cell lines to identify the transcription factor (TF) POU2F3 (POU class 2 homeobox 3; also known as SKN-1a/OCT-11) as a powerful dependency in a subset of SCLC lines. An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Using chromatin- and RNA-profiling experiments, we provide evidence that POU2F3 is a master regulator of tuft cell identity in a variant form of SCLC. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Our CRISPR screens exposed other unique dependencies in POU2F3-expressing SCLC lines, including the lineage TFs SOX9 and ASCL2 and the receptor tyrosine kinase IGF1R (insulin-like growth factor 1 receptor). These data reveal POU2F3 as a cell identity determinant and a dependency in a tuft cell-like variant of SCLC, which may reflect a previously unrecognized cell of origin or a trans-differentiation event in this disease.
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Comprehensive genomic profiles of small cell lung cancer
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A single-cell survey of the small intestinal epithelium
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Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit
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Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites
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Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut
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Small-cell lung cancer: what we know, what we need to know and the path forward
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Baine, M. K., Hsieh, M.-S., Lai, W. V., Egger, J. V., Jungbluth, A. A., Daneshbod, Y., Beras, A., Spencer, R., Lopardo, J., Bodd, F., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.09.009 · Cited by 522
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Megyesfalvi, Z., Gay, C. M., Popper, H., Pirker, R., Ostoros, G., Heeke, S., Lang, C., Hoetzenecker, K., Schwendenwein, A., Boettiger, K., et al. (2023) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21785 · Cited by 369
Metadata
- Authors
- Huang, Y.-H., Klingbeil, O., He, X.-Y., Wu, X. S., Arun, G., Lu, B., Somerville, T. D. D., Milazzo, J. P., Wilkinson, J. E., Demerdash, O. E., Spector, D. L., Egeblad, M., Shi, J., & Vakoc, C. R.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2018-06-26
- Volume
- 32
- Issue
- 13-14
- Pages
- 915-928
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2810630532
- Cited by
- 422
- References
- 36
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Huang, Y.-H., Klingbeil, O., He, X.-Y., Wu, X. S., Arun, G., Lu, B., Somerville, T. D. D., Milazzo, J. P., Wilkinson, J. E., Demerdash, O. E., Spector, D. L., Egeblad, M., Shi, J., & Vakoc, C. R. (2018). POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer. Genes & Development. https://doi.org/10.1101/gad.314815.118
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