Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages Data and Software Availability PXD007996 GSE67922 Article Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages

Abstract

Graphical Abstract Highlights d mTORC1 regulates CCL2 expression via FOXK1 activation d FOXK1 is dephosphorylated and thereby activated in response to mTORC1 activation d The mTORC1-FOXK1-CCL2 pathway is independent of classical NF-kB signaling d This pathway promotes macrophage accumulation and associated tumor growth Authors Hirokazu Nakatsumi, Masaki Matsumoto, Keiichi I. Nakayama Correspondence nakayak1@bioreg.kyushu-u.ac.jp In Brief Nakatsumi et al. show that mTORC1 regulates CCL2 expression in a manner independent of NF-kB signaling by dephosphorylating the transcription factor FOXK1. Moreover, they demonstrate that hyperactivation of mTORC1 results in attraction of M2-type tumor-associated macrophages and promotes tumor growth in vivo via the mTORC1-FOXK1-CCL2 pathway.