Rabbit Anti-Human ANGPTL4 (a.a. 331-406) Polyclonal antibody

Metastatic cancer cells acquire energy-intensive processes including increased invasiveness and chemoresistance. However, how the energy demand is met and the molecular drivers that coordinate an increase in cellular metabolic activity to drive epithelial-mesenchymal transition (EMT), the first step of metastasis, remain unclear. Using different in vitro and in vivo EMT models with clinical patient's samples, we showed that EMT is an energy-demanding process fueled by glucose metabolism-derived adenosine triphosphate (ATP). We identified angiopoietin-like 4 (ANGPTL4) as a key player that coordinates an increase in cellular energy flux crucial for EMT via an ANGPTL4/14-3-3. signaling axis. This augmented cellular metabolic activity enhanced metastasis. ANGPTL4 knockdown suppresses an adenylate energy charge elevation, delaying EMT. Using an in vivo dualinducible EMT model, we found that ANGPTL4 deficiency reduces cancer metastasis to the lung and liver. Unbiased kinase inhibitor screens and Ingenuity Pathway Analysis revealed that ANGPTL4 regulates the expression of 14-3-3. adaptor protein via the phosphatidylinositol-3-kinase/AKT and mitogen-activated protein kinase signaling pathways that culminate to activation of transcription factors, CREB, cFOS and STAT3. Using a different mode of action, as compared with protein kinases, the ANGPTL4/14-3-3. signaling axis consolidated cellular bioenergetics and stabilized critical EMT proteins to coordinate energy demand and enhanced EMT competency and metastasis, through interaction with specific phosphorylation signals on target proteins.

Elevated plasma lipid levels are linked to atherosclerosis, a hallmark for coronary artery disease (CAD), documented by animal studies as well as angiographic and clinical studies. The ability to treat hyperlipidemia through lifestyle changes and lipid-lowering agents has been related to the slow progression of atherosclerosis and decreased incidence of major coronary events. Angiopoietin-like proteins (ANGPTLs) are a family of secreted glycoproteins expressed in the liver that share common domain characteristics with angiopoietins, the main regulators of angiogenesis. Although ANGPTLs cannot bind the angiopoietin receptors expressed on endothelial cells, 2 ANGPTL family members (ANGPTL3 and ANGPTL4) have clinical importance because of their unambiguous effects on lipoprotein metabolism in mice and humans. The regulation of plasma lipid levels by ANGPTL3 is controlled via affecting lipoprotein lipase and endothelial lipase-mediated hydrolysis of triglycerides (TGs) and phospholipids. ANGPTL 3, along with the other 2 members, 4 and 8, is a key to balancing the distribution of circulating TGs between white adipose tissue (WAT) and oxidative tissues. Thus, ongoing trials with newly discovered medications in the form of monoclonal antibodies or antisense oligonucleotides with novel targets are under analysis and may represent a fresh frontier in the treatment of hyperlipidemia and CAD.