title: Macrophage migration inhibitory factor promotes breast cancer metastasis via activation of HMGB1/TLR4/NF kappa B axis.
abstract: Macrophage migration inhibitory factor (MIF) is up-regulated in diverse solid tumors and acts as the critical link between immune response and tumorigenesis. In this study, we demonstrated that MIF overexpression promoted migration of breast cancer cells by elevating TLR4 expression. Further investigation evidenced that MIF induced ROS generation. MIF-induced ROS led to ERK phosphorylation, which facilitated HMGB1 release from the nucleus to the cytoplasm. MIF overexpression also induced caveolin-1 phosphorylation. Caveolin-1 phosphorylation contributed to HMGB1 secretion from the cytoplasm to the extracellular matrix. The extracellular HMGB1 activated TLR4 signaling including NF-κB phosphorylation, which was responsible for the transcription of Snail and Twist as well as MMP2 activation. Furthermore, MIF-induced caveolin-1-dependent HMGB1 secretion might control the recruitment of CD11b+ immune cells. Our data suggested that MIF affected the intrinsic properties of tumors and the host immune response in tumor microenvironment by regulating the TLR4/HMGB1 axis, leading to metastasis of breast cancer.
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Yanliang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Xungeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China. Electronic address: txs0509@163.com.
authors.forename: Xingsong
authors.initials: X
authors.lastname: Tian
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000235:genetics*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D009362:Neoplasm Metastasis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics*; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D024243:HMGB1 Protein; D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Breast cancer; HMGB1; Macrophage migration inhibitory factor (MIF); Metastasis; TLR4