Leptin, a peptide hormone secreted from white adipocytes, may be an independent risk factor for breast cancer.Here, we treated suberoylanilide hydroxamic acid (SAHA) on Leptin-induced cell proliferation and invasion in the estrogen-receptor-positive breast cancer cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231.
Leptin seems to play a crucial role during the first stages of pregnancy as it modulates critical processes such as proliferation, protein synthesis, invasion and apoptosis in placental cells.
Additionally, we also determined the effect of leptin on the epithelial-mesenchymal transition (EMT) bio-markers, in vitro invasion and sphere-formation of MCF-7 and ZR-75-1 cell lines.
Here, we aimed to investigate the effect of leptin on the proliferation, migration and invasion of breast cancer cells, as well as to elucidate its underlying mode of action.
In addition, leptin induces transactivation of ErbB-2, and interacts in triple negative breast cancer cells with insulin like growth factor-1 (IGF-1) to transactivate the epidermal growth factor receptor (EGFR), thus promoting invasion and migration.
In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloprotease secretion, and invasion.
Indeed, pathological remodelling of white adipose tissue and increased levels of fat-specific cytokines (mainly leptin), as a consequence of the obesity condition, have been associated with several hallmarks of breast cancer, such as sustained proliferative signaling, cellular energetics, inflammation, angiogenesis, activating invasion and metastasis.
Notably, coimmunoprecipitation analysis indicated that leptin enhanced the interaction of MT1-MMP with KIF1B in a time-dependent manner, which consequently contributed to GC cell invasion.
Our findings suggest that leptin enhances the invasion of pancreatic cancer through the increase in MMP-13 production, and targeting the leptin/MMP-13 axis could be an attractive therapeutic strategy for pancreatic cancer.
Our results indicated that leptin served as a key intermediary linking the accumulation of excess adipokine to the invasion of glioma stem-like cells, which may be a novel therapeutic target for suppressing tumor invasion and recurrence.