Abstract:
:Macrophages are abundant in the tumor microenvironment. They are highly plastic and able to acquire pro-tumoral phenotypes in response to microenvironmental stimuli. When we treated RAW 264.7 macrophages with inhibitors of various oncogenic pathways, we found that the focal adhesion kinase (FAK) inhibitors PF573228 and TAE226 could induce cell multinucleation by suppressing furrowing and cytokinesis. This failure in cytokinesis involves Rac1, whose activity is elevated by FAK inhibitors, and the p21-activated kinases, comprising the downstream effectors of Rac. We also investigated the influence of cell multinucleation on macrophage physiology in RAW 264.7 cells. This is the first study to report that FAK inhibitors suppress furrow ingression and early cytokinesis. Of note, we found that FAK inhibitors caused a dramatic increase in pro-tumoral cytokines in multinuclear cells, suggesting the potential to convert macrophages into pro-tumoral phenotypes.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
He X,Chen X,Li B,Ji J,Chen Sdoi
10.1002/1873-3468.12895subject
Has Abstractpub_date
2017-12-01 00:00:00pages
3861-3871issue
23eissn
0014-5793issn
1873-3468journal_volume
591pub_type
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