title: Daintain/AIF-1 promotes breast cancer cell migration by up-regulated TNF-α via activate p38 MAPK signaling pathway.
abstract: Tumor-associated macrophages can release a vast diversity of growth factors, proteolytic enzymes, cytokines, and inflammatory mediators. Many of these factors are key agents in cancer metastasis. Daintain/AIF-1 is a macrophage-derived inflammatory cytokine which defined a distinct subset of tumor-associated activated macrophages/microglial cells. Previous study demonstrated that daintain/AIF-1 could promote breast cancer proliferation through activating NF-κB/cyclin D1 pathway and facilitate tumor growth. However, the effect of Daintain/AIF-1 on cell migration and cancer metastasis has never been reported. Herein, we used a mimic tumor microenvironment by incubating breast cancer cell lines, MDA-MB-231 and MCF-7 cells, with macrophage-conditioned medium with or without purified daintain/AIF-1 polypeptide to evaluate cell migration. Results indicated that daintain/AIF-1 enhanced the migration of MDA-MB-231 and MCF-7 cells in the manner of TNF-α up-regulation. Further study found that daintain/AIF-1 activates p38 MAPK signaling pathway contributing to up-regulation of TNF-α in MDA-MB-231 and MCF-7 cells. Therefore, this novel daintain/AIF-1-p38-TNF-α pathway and insight into daintain/AIF-1 might have potential benefits in the control of tumor metastasis during cancer therapy.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Feng
authors.forename: Shaohui
authors.initials: S
authors.lastname: Jia
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Du
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Zhengwang
authors.initials: Z
authors.lastname: Chen
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008840:Microfilament Proteins; D034622:RNA Interference; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells; D015854:Up-Regulation / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases