Leptin activates Akt in oesophageal cancer cells via multiple atorvastatin-sensitive small GTPases.

Leptin activates Akt in oesophageal cancer cells via multiple atorvastatin-sensitive small GTPases. Mol Cell Biochem. 2021 Feb 13;: Authors: Beales ILP, Ogunwobi OO Abstract Obesity is a risk factor for Barrett's oesophagus and oesophageal adenocarcinoma. Adipose tissue secretes the hormone leptin. Leptin is a growth factor for several cell types, including Barrett's cells and oesophageal adenocarcinoma cells. Statins are associated with reduced rates of Barrett's oesophagus and oesophageal cancer and exhibit anti-cancer effects in vitro. The mechanisms of these effects are not fully established. We have examined the effects of leptin and the lipid-soluble statin, atorvastatin, on signalling via monomeric GTP-binding proteins and Akt. Proliferation and apoptosis were assessed in OE33 cells. Akt activity was quantified by cell-based ELISA and in vitro kinase assay. Specific small-molecule inhibitors and a dominant-negative construct were used to reduce Akt activity. Small GTPases were inhibited using transfection of dominant-negative plasmids, prenylation inhibitors and pretreatment with atorvastatin. Leptin stimulated Akt activity and cell proliferation and inhibited camptothecin-induced apoptosis in an Akt-sensitive manner. Leptin induced phosphorylation of Bad and FOXO1 in an Akt-sensitive manner. Leptin activated Ras, Rac, RhoA and cdc42. Transfection of dominant-negative plasmids confirmed that leptin-induced Akt activation requi...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Tags: Mol Cell Biochem Source Type: research