Leptin induces matrix metalloproteinase 7 expression to promote ovarian cancer cell invasion by activating ERK and JNK pathways

Abstract

Leptin, an adipokine secreted by adipose tissue, induces cell invasion and metastasis. MMP7 is a member of the matrix metalloproteinase family that plays an important role in cell invasion. Here we evaluate the possible role and underlying mechanism of MMP7 in the leptin-mediated cell invasion in ovarian cancer cell lines. All experiments were carried out in cultured SKOV3, OVCAR3, and CaoV-3 ovarian cell lines. MMP7 expression was determined using the Western blot following treatment to various concentrations of leptin for defined time intervals. The activation of ERK, JNK, and P38 MAP kinases were determined using Western blotting. Wound healing and BD matrigel invasion assays were used to measure cell migration and invasion. The siRNA approach and pharmacological inhibitors of ERK and JNK pathway were used to confirm the receptor-dependent effect of leptin and a role for ERK and JNK pathway. Zymography assay was employed to determine MMP2 and MMP9 activation. Results show that leptin induces ERK1/2 and JNK1/2 activation and subsequently promotes MMP7 expression in SKOV3 (4.8 ± 0.14 fold of control, P < 0.01) and OVCAR3 (3.1 ± 0.19 fold of control, P < 0.01) ovarian cancer cell lines. These effects was reversed by knockdown of OB-Rb and/or pre-incubation with PD98059 (ERK1/2 inhibitor), SP600125 (JNK1/2 inhibitor). Gelatin zymography showed that MMP7 gene silencing attenuated leptin-induced MMP9 activation in SKOV3 cell line. Taken together, our results suggest new evidences for a modulatory effect of leptin in regulation of ovarian cancer cell invasion by stimulating MMP7 expression via ERK and JNK pathways.

PCNA and JNK1‐Stat3 pathways respectively promotes and inhibits diabetes‐associated centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex in human colon cancer HCT116 cells

“…In addition to the regulation of whole‐body fatty acid homeostasis, adipose tissue functions as a complex endocrine organ, secreting adipokines, such as leptin, adiponectin, visfatin, tumor necrosis factor‐α, interleukin‐6, monocyte chemotactic protein‐1, and adipocyte fatty acid‐binding protein (Hsu, Wu, Chang, & Lin, ). Leptin induces matrix metalloproteinase 7 expression to promote ovarian cancer cell invasion by activating ERK and JNK pathways (Ghasemi, Hashemy, Aghaei, & Panjehpour, ). Genistein inhibited JNK activation, which inhibited the TNF‐α‐mediated downregulation of adiponectin (Yanagisawa et al, ).…”

Mitochondria‐mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase

“…Comparisons of the three samples identified 581, 220, and 441 DEGs in pairs of CO/OE, CO/OS, and OE/OS, respectively ( Figure 5A-C). 25,26 These common DEGs may play an important role in relative cancer pathways, cell cycle, and apoptosis. To further improve the accuracy of results, the new genes of DEGs were filtered from the whole DEGs.…”

Comprehensive analysis of mRNA‐level and miRNA‐level subpathway activities for identifying robust ovarian cancer prognostic signatures

“…was involved, was also enriched in the OvCa long survival event. 31 For mRNA-level risk results, the overexpression of retinol binding protein 4 (RBP4) in OvCa cells promoted cancer cell migration and proliferation, 32 and an adipokine secreted by adipose tissue also induced cell invasion and metastasis, 33 which showed the potential risk roles of path: 04920_2 (Adipocykine signalling pathway, top 1). For path: 04360_5 (Axon guidance, top 2), a previous transcriptome-based study also revealed the axon guidance molecules were related with OvCa clinical prognosis.…”