Breast Cancer Research and Treatment

, Volume 131, Issue 3, pp 891–898 | Cite as

Daintain/AIF-1 promotes breast cancer cell migration by up-regulated TNF-α via activate p38 MAPK signaling pathway

  • Tao Li
  • Zhiguo Feng
  • Shaohui Jia
  • Wei Wang
  • Zhongxia Du
  • Ning Chen
  • Zhengwang Chen
Preclinical Study


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.


Inflammatory cytokine Daintain/AIF-1 TNF-α Breast cancer cell p38 MAPK Cell migration 



Nuclear factor-κB


Mitogen-activated protein kinase


Tumor necrosis α


Conditioned medium


siRNA knockdown of daintain/AIF-1 in U937 cell


Epithelial–mesenchymal transition



This work was supported by the National Science Foundation of China (Grants 30370647 and 30470823) and Chinese 863 Program (2002AA214061).


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Tao Li
    • 1
  • Zhiguo Feng
    • 1
    • 2
  • Shaohui Jia
    • 1
  • Wei Wang
    • 1
  • Zhongxia Du
    • 1
  • Ning Chen
    • 3
  • Zhengwang Chen
    • 1
  1. 1.Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.College of Life ScienceXinyang Normal UniversityXinyangPeople’s Republic of China
  3. 3.The Cancer Institute of New JerseyNew BrunswickUSA

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