Abstract:

Objective To investigate the underlying mechanism by which long train acyl⁃CoA synthetases （ACSL4）regulates the expression of cyclooxygenase ⁃2（COX2）to promote breast cancer cell metastasis. Methods ACSL4 was overexpressed or knocked down in breast cancer cells with different invasive breast cancer phenotypes. Wound healing assay and Transwell assay were used to examine the invasive ability of cells. The relationship between ACSL4 and related genes was analyzed by using TCGA database. The regulation of COX2 by ACSL4 was verified by qPCR and Western blotting. The secretion of prostaglandin E2（PGE2）in breast cancer cells was detected by ELISA. Results In TCGA database，ACSL4 was positively correlated with COX2 expression（r = 0.15，P < 0.05）. Overexpression of ACSL4 in low⁃invasive breast cancer cells MCF⁃7 significantly increased the invasion ability of the cells and the expression of COX2 and Vimentin. Knockdown of ACSL4 in MDA⁃MB⁃231 cells significantly reduced the invasion ability of the cells and the expression of COX2 and Vimentin. ELISA assay showed that knock⁃ down of ACSL4 reduced the level of PGE2，a metabolite catalyzed by COX2，while overexpression of ACSL4 increased the level of PGE2. Conclusion ACSL4 promotes the secretion of PGE2 by increasing COX2 expression， which results in enhanced invasive potential of breast cancer cells. Our results provide a new experimental evidence and strategy for the clinical treatment of breast cancer metastasis.

Key words:

ACSL4, COX2, PGE2, breast cancer, invasion and metastasis