Activating transcription factor 4 (ATF4), an endoplasmic reticulum 
stress-inducible transcription factor, plays important roles in cancer 
progression and resistance to therapy. However, no report is available about its 
roles in endometrial cancer (EC). In this study, we found that ATF4 is commonly 
expressed in EC cell lines. Loss-of-function studies in two EC cell lines showed 
that ATF4 knockdown suppresses tumor growth of EC in vivo without influencing 
cell proliferation in vitro. And xenograft tumors derived from ATF4-knockdown 
cells had reduced M2 macrophage infiltration. In clinical specimens, ATF4-high 
expressing tumors indeed contained more macrophage infiltration compared to 
those with lower ATF4 expression. Moreover, we identified that ATF4-mediated 
chemokine CCL2 expression ultimately results in macrophage infiltration and 
tumor growth of EC. Taken together, our findings suggest that ATF4 contributes 
to tumor growth of EC by promoting CCL2 and subsequent recruitment of 
macrophage, and that ATF4/CCL2 axis might be a potential therapeutic target for 
EC.