Lumican promotes proliferation, migration and invasion of gastric cancer through ERK pathway

Abstract

Abstract Purpose To clarify the molecular mechanism of lumican's effects on gastric cancer cell proliferation, migration, and invasion. Methods qRT-PCR was used to analyze lumican expression in gastric cancer tissues and cell lines. Small interfering RNA (siRNA) transfection and lentivirus infection have been used to produce lumican knockdown or overexpression gastric cancer cell models from screened cell lines. CCK-8, wound healing assays, and transwell assays were performed to confirm the effect of lumican on gastric cancer cell’s proliferation, migration, and invasion. To further evaluate the potencial mechnism of lumican on gastric cancer cells, bioinformatic prediction and western blot experiment were used to identify and confirm its related signaling pathway. Results Using MGC-803 and AGS gastric cancer cells, lumican knockdown or overexpression was achieved. Overexpression of lumican increased MGC-803 and AGS gastric cancer cell proliferation, migration, and invasion, whereas knockdown decreased them. The expression levels of ERK and p-ERK, two key proteins of the ERK pathway, were significantly decreased in MGC-803 and AGS cells with lumican knockdown, while the opposite result was observed with lumican overexpression; the expression levels of MEK and p-MEK, two key proteins of the MEK pathway, were not significantly changed with lumican knockdown or overexpression. GDC-0994, an ERK pathway inhibitor, restored ERK1/2 and p-ERK1/2 protein expression in MGC-803 and AGS cells overexpressing lumican. Conclusion Lumican was discovered in high levels in the tissues of patients with gastric cancer, and it promoted proliferation, migration, and invasion in gastric cancer cells. Lumican may impact the expression of two main proteins, ERK1/2 and p-ERK1/2, in the ERK signaling pathway rather than activating it via MEK, indicating that the pathway may be a therapeutic target for lumican overexpression in gastric cancer.