Lung Cancer Induces NK Cell Contractility and Cytotoxicity Through Transcription Factor Nuclear Localization.

Autor:	Wong DCP; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.; Mechanobiology Institute Singapore, National University of Singapore, Singapore, Singapore., Lee EHC; Department of Biological Sciences, National University of Singapore, Singapore, Singapore., Er J; Department of Biological Sciences, National University of Singapore, Singapore, Singapore., Yow I; Mechanobiology Institute Singapore, National University of Singapore, Singapore, Singapore., Koean RAG; Department of Biological Sciences, National University of Singapore, Singapore, Singapore., Ang O; Department of Biological Sciences, National University of Singapore, Singapore, Singapore., Xiao J; Mechanobiology Institute Singapore, National University of Singapore, Singapore, Singapore., Low BC; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.; Mechanobiology Institute Singapore, National University of Singapore, Singapore, Singapore.; University Scholars Programme, National University of Singapore, Singapore, Singapore., Ding JL; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.; Integrative Sciences and Engineering Programme, National University of Singapore, Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 May 16; Vol. 10, pp. 871326. Date of Electronic Publication: 2022 May 16 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.871326
Abstrakt:	Actomyosin-mediated cellular contractility is highly conserved for mechanotransduction and signalling. While this phenomenon has been observed in adherent cell models, whether/how contractile forces regulate the function of suspension cells like natural killer (NK) cells during cancer surveillance, is unknown. Here, we demonstrated in coculture settings that the evolutionarily conserved NK cell transcription factor, Eomes, undergoes nuclear shuttling during lung cancer cell surveillance. Biophysical and biochemical analyses revealed mechanistic enhancement of NK cell actomyosin-mediated contractility, which is associated with nuclear flattening, thus enabling nuclear entry of Eomes associated with enhanced NK cytotoxicity. We found that NK cells responded to the presumed immunosuppressive TGFβ in the NK-lung cancer coculture medium to sustain its intracellular contractility through myosin light chain phosphorylation, thereby promoting Eomes nuclear localization. Therefore, our results demonstrate that lung cancer cells provoke NK cell contractility as an early phase activation mechanism and that Eomes is a plausible mechano-responsive protein for increased NK cytotoxicity. There is scope for strategic application of actomyosin-mediated contractility modulating drugs ex vivo, to reinvigorate NK cells prior to adoptive cancer immunotherapy in vivo (177 words). Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Wong, Lee, Er, Yow, Koean, Ang, Xiao, Low and Ding.)
Databáze:	MEDLINE
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