ABCA8 promotes migration and invasion of human pancreatic cancer cells by activating ERK signaling pathway / 肿瘤

ABSTRACT

Objective: To investigate the effects of ABC-binding cassette transporter A subfamily 8 (ABCA8) on the migration and invasion of pancreatic cancer cells and the possible mechanism. Methods: Human pancreatic cancer CFPAC-1 cells were infected with the lentivirus GV358 carrying ABCA 8 gene or the empty vector lentivirus to establish ABCA8 overexpression cells or the control cells, respectively. The ABCA8 overexpression was confirmed by real-time fluorescent quantitative PCR and Western blotting. The effects of ABCA8 overexpression on the migration and invasion of CFPAC-1 cells were analyzed by wound healing assay and Transwell assay, respectively. The expression levels of extracellular signal-regulated kinase (ERK) and phospho-ERK (p-ERK) in ABCA8-overexpressed CFPAC-1 cells were detected by Western blotting. The effects of inhibiting ERK signaling by SCH772984 on ABCA8-mediated migration and invasion of CFPAC-1 cells were detected by Transwell assay. The expression levels of matrix metalloproteinases 2 (MMP2), MMP7, MMP9 and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNAs in ABCA8-overexpressed CFPAC-1 cells were detected by real-time fluorescent quantitative PCR, and the expression levels of MMP7 and TIMP1 mRNAs in ABCA8-overexpressed CFPAC-1 cells treated with SCH772984 were detected by real-time fluorescent quantitative PCR. Results: ABCA8-overexpressed CFPAC-1 cells were successfully established. ABCA8 overexpression significantly promoted the migration (P 0.01) and invasion (P 0.05) of CFPAC-1 cells. The expression level of p-ERK protein was significantly elevated in ABCA8-overexpressed CFPAC-1 cells (P 0.01), and ERK inhibitor SCH772984 could eliminate the changes of ABCA8-induced migration and invasion of CFPAC-1 cells (both P 0.05). Meanwhile, ABCA8 overexpression could significantly upregulate MMP7 expression level (P 0.001) and downregulate TIMP1 expression level (P 0.01) in CFPAC-1 cells, and ERK inhibitor SCH772984 could eliminate the changes of MMP7 and TIMP1 expression levels induced by ABCA8 overexpression (both P 0.05). Conclusion: ABCA8-induced ERK signaling activation can enhance the migratory and invasive properties of human pancreatic cancer cells, which may be related to the upregulation of MMP7 expression and the downregulation of TIMP1 expression.