The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1)
Open accessAbstract
The mechanisms of malignant cell transformation caused by the oncogenic, chimeric nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) remain only partially understood, with most of the previous studies focusing mainly on the impact of NPM/ALK on cell survival and proliferation. Here we report that the NPM/ALK-carrying T cell lymphoma (ALK+TCL) cells strongly express the immunosuppressive cell-surface protein CD274 (PD-L1, B7-H1), as determined on the mRNA and protein level. The CD274 expression is strictly dependent on the expression and enzymatic activity of NPM/ALK, as demonstrated by inhibition of the NPM/ALK function in ALK+TCL cells by the small molecule ALK inhibitor CEP-14083 and by documenting CD274 expression in IL-3-depleted BaF3 cells transfected with the wild-type NPM/ALK, but not the kinase-inactive NPM/ALK K210R mutant or empty vector alone. NPM/ALK induces CD274 expression by activating its key signal transmitter, transcription factor STAT3. STAT3 binds to the CD274 gene promoter in vitro and in vivo , as shown in the gel electromobility shift and chromatin immunoprecipitation assays, and is required for the PD-L1 gene expression, as demonstrated by siRNA-mediated STAT3 depletion. These findings identify an additional cell-transforming property of NPM/ALK and describe a direct link between an oncoprotein and an immunosuppressive cell-surface protein. These results also provide an additional rationale to therapeutically target NPM/ALK and STAT3 in ALK+TCL. Finally, they suggest that future immunotherapeutic protocols for this type of lymphoma may need to include the inhibition of NPM/ALK and STAT3 to achieve optimal clinical efficacy.
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Cites
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Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
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Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.36 · Cited by 2,733
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The PD‐1 pathway in tolerance and autoimmunity
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Metadata
- Authors
- Marzec, M., Zhang, Q., Goradia, A., Raghunath, P. N., Liu, X., Paessler, M., Wang, H. Y., Wysocka, M., Cheng, M., Ruggeri, B. A., & Wasik, M. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-12-30
- Volume
- 105
- Issue
- 52
- Pages
- 20852-20857
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2051083170
- Cited by
- 728
- References
- 36
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). https://app.cochat.ai/papers/10.1073/pnas.0810958105
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- Marzec, M., Zhang, Q., Goradia, A., Raghunath, P. N., Liu, X., Paessler, M., Wang, H. Y., Wysocka, M., Cheng, M., Ruggeri, B. A., & Wasik, M. A. (2008). Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0810958105
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
