FAK inhibitors induce cell multinucleation and dramatically increase pro-tumoral cytokine expression in RAW 264.7 macrophages.

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 Lett

journal_title

FEBS letters

authors

He X,Chen X,Li B,Ji J,Chen S

doi

10.1002/1873-3468.12895

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

3861-3871

issue

23

eissn

0014-5793

issn

1873-3468

journal_volume

591

pub_type

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