Role of leptin up-regulated GRP78 expression in migration of lung cancer cells

Abstract

Objective To investigate the effect of leptin on the migration of lung cancer cell lines A549 and H460 and the potential mechanisms. Methods The GEPIA website was used to analyze the correlation of the expression levels of leptin and glucose-regulated protein-78 (GRP78) with overall survival rate in lung cancer patients from TCGA database. Wound healing assay was used to detect the effect of leptin and HA15 (GRP78 targeting inhibitor) on the migration of lung cancer A549 and H460 cells; Immunofluorescence assay was used to measure the expression of GRP78 in lung cancer cells. Finally, lung cancer A549 cells were treated with PI3K targeting inhibitor Ly294002, mTOR targeting inhibitor rapamycin alone or in combination with leptin, and then Western blot assay was used to investigate the impact of leptin on PI3K/mTOR/STAT3 signaling pathway and GRP78 expression. Results Survival analysis showed that high expression of leptin or GRP78 was closely related to decreased overall survival rate in lung cancer patients (P < 0.05). Wound healing test indicated that leptin enhanced the migration of lung cancer A549 and H460 cells (P < 0.05). Immunofluorescence assay displayed that leptin upregulated GRP78 expression in A549 and H460 cells (P < 0.01). Western blot assay suggested that leptin could upregulate the expression of GRP78 in lung cancer A549 cells through PI3K/mTOR/STAT3 signaling pathway (P < 0.001). Wound healing test showed inhibition of GRP78 attenuated the effect of leptin on promoting migration. Conclusion Leptin promotes the migration of lung cancer cells by up-regulating GRP78 through PI3K/mTOR/STAT3 signaling pathway.

Keywords

• leptin
• lung cancer
• glucose-regulated protein-78
• migration