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An HLA-G/SPAG9/STAT3 axis promotes brain metastases

Bassey-Archibong, Blessing Iquo; Rajendra Chokshi, Chirayu; Aghaei, Nikoo; Kieliszek, Agata Monika; Tatari, Nazanin; McKenna, Dillon; Singh, Mohini; ... Singh, Sheila Kumari; + view all (2023) An HLA-G/SPAG9/STAT3 axis promotes brain metastases. Proceedings of the National Academy of Sciences (PNAS) , 120 (8) , Article e2205247120. 10.1073/pnas.2205247120. Green open access

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Abstract

Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing the need for a better understanding of the disease. Herein, we analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the brain metastatic cascade-the "premetastatic" or early stage when they first colonize the brain and the established macrometastatic stage. RNA sequencing was used to obtain the transcriptional profiles of premetastatic and macrometastatic (non-premetastatic) lung, breast, and melanoma BMICs. We identified that lung, breast, and melanoma premetastatic BMICs share a common transcriptomic signature that is distinct from their non-premetastatic counterparts. Importantly, we show that premetastatic BMICs exhibit increased expression of HLA-G, which we further demonstrate functions in an HLA-G/SPAG9/STAT3 axis to promote the establishment of brain metastatic lesions. Our findings suggest that unraveling the molecular landscape of premetastatic BMICs allows for the identification of clinically relevant targets that can possibly inform the development of preventive and/or more efficacious BM therapies.

Type: Article
Title: An HLA-G/SPAG9/STAT3 axis promotes brain metastases
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.2205247120
Publisher version: https://doi.org/10.1073/pnas.2205247120
Language: English
Additional information: Copyright © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Keywords: HLA-G, SPAG9, STAT3, brain metastases, Adult, Humans, HLA-G Antigens, Brain Neoplasms, Lung, Brain, Melanoma, Lung Neoplasms, Adaptor Proteins, Signal Transducing, STAT3 Transcription Factor
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10165283
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