The mechanism of tumor necrosis factor-α in promoting breast cancer metastasis

Objective Tumor necrosis factor-α (TNF-α) , as one of the inflammatory factors, plays an important role in the oncogenesis and development of tumors. This study aimed to explore the mechanism of TNF-α in promoting breast cancer metastasis. Methods Plasma TNF-α levels of 53 breast cancer patients were detected by enzyme-linked immunosorbent assay (ELISA) . The migration ability of MDA-MB-231 breast cancer cells treated with vehicle, TNF-α, transfected with vector, Arf6-T27N, vectorplus TNF-α, Arf6-T27N plus TNF-α was detected by wound healing assay. TNF-α-induced activization of small G proteins of MDA-MB-231 cells treated with vehicle or TNF-α was screened and detected by small G protein activation assay (GLISA) . The comparison of means between the two groups was performed using t-test. The comparison of means between multiple groups was performed using a one-way analysis of variance, and the LSD test was used in the post hoc comparisons. The relationships between the levels of TNF-α and clinicopathological parameters were analyzed by χ2 test or Fisher exact probability method. Results Compared with breast cancer patients without lymph node metastasis, the plasma levels of TNF-α in patients with lymph node metastasis were significantly increased (709.58±277.51 vs 391.24±307.35, P< 0.001) .Wound healing assay showed that TNF-α could significantly promote the migration of MDA-MB-231 cells compared to the control cells (2.34±0.25 vs 1.00±0.04, P< 0.001) . TNF-α notably activatedthe small G protein Arf6 compared to the control group (3.11±0.14 vs 1.00±0.02, P< 0.001) , and overexpressed Arf6 (Arf6-T27N) significantly inhibited TNF-α-induced migration of breast cancer cells compared to theTNF-α-treatedcells (1.83±0.15 vs 2.33±0.14, P< 0.001) . Conclusion This study demonstrates that TNF-α promotes breast cancer cell migration by activating Arf6, suggesting that TNF-α/Arf6 might be used as a new target for controlling breast cancer metastasis. Key words: TNF-α; Arf6; Breast cancer; Lymph node metastasis