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However, the crosstalk between M2\u2010polarized tumor\u2010associated macrophages (M2\u2010TAMs) and intrahepatic cholangiocarcinoma (ICC) remains undetermined. In the present study, we aimed to clarify the role of M2\u2010TAMs in ICC and the underlying mechanism. The in vitro assay demonstrated M2\u2010TAMs promoted epithelial\u2010mesenchymal transition (EMT) of ICC cells, resulting in enhanced cell invasion and metastasis ability. Moreover, M2\u2010TAMs modulated the microenvironment of ICC by increasing the secretion of cytokines (GM\u2010CSF, tumor necrosis factor\u2010\u03b1 [TNF\u2010\u03b1], ICAM\u20101, interleukin\u20106 [IL\u20106], etc) and chemokines (CCL1, CCL3, etc). In addition, p\u2010AKT (Ser473) and p\u2010PRAS40 (Thr246) were upregulated in ICC cells when cocultured with M2\u2010TAMs or treated with M2\u2010TAMs secreted core cytokines (GM\u2010CSF, TNF\u2010\u03b1, ICAM\u20101, and IL\u20106). Consistently, AKT3 silencing (but not AKT1 silencing and AKT2 silencing) markedly inhibited phosphorylation of AKT and PRAS40 of ICC cells and inhibited the EMT process when cocultured with M2\u2010TAMs. Taken together, the current data indicated that M2\u2010TAMs promoted ICC cells EMT, partially through increasing secretion of cytokines and chemokines, thus modulating the microenvironment and activating the AKT3\/PRAS40 signaling pathway.<\/jats:p>","DOI":"10.1002\/jcb.29514","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T12:55:58Z","timestamp":1573044958000},"page":"2828-2838","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["M2\u2010polarized tumor\u2010associated macrophages promote epithelial\u2010mesenchymal transition via activation of the AKT3\/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma"],"prefix":"10.1002","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5278-4706","authenticated-orcid":false,"given":"Dalong","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Disease  Shanghai China"},{"name":"Department of Gastroenterology and Hepatology, Xiamen Branch, Zhongshan Hospital Fudan University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiancheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Disease  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine The University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Disease  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuncai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Disease  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Disease  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. 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