PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 Nature Research
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190332
- 본문언어 영어
- Published As https://doi.org/10.1038/s41467-022-29471-6
- PubMed https://pubmed.ncbi.nlm.nih.gov/35365657
초록/요약
Myeloid cells play key roles in cancer immune suppression and tumor progression. In response to tumor derived factors, circulating monocytes and granulocytes extravasate into the tumor parenchyma where they stimulate angiogenesis, immune suppression and tumor progression. Chemokines, cytokines and interleukins stimulate PI3Kγ-mediated Rap1 activation, leading to conformational changes in integrin α4β1 that promote myeloid cell extravasation and tumor inflammation Here we show that PI3Kγ activates a high molecular weight form of myosin light chain kinase, MLCK210, that promotes myosin-dependent Rap1 GTP loading, leading to integrin α4β1 activation. Genetic or pharmacological inhibition of MLCK210 suppresses integrin α4β1 activation, as well as tumor inflammation and progression. These results demonstrate a critical role for myeloid cell MLCK210 in tumor inflammation and serve as basis for the development of alternative approaches to develop immune oncology therapeutics. © 2022, The Author(s).
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