Role of microsomal triglyceride transfer protein (MTP) in tumor growth. A new function for MTP?

QUIROGA, AD

Congreso; SAIB - SAMIGE Joint meeting 2021 on line; 2021

Microsomal triglyceride transfer protein (MTP)was first identified as a cellular protein capable of transferring neutrallipids between membrane vesicles in vitro. Later, its role as an essentialchaperone for the biosynthesis of apolipoprotein B-containing triglyceride-richlipoproteins was established. Now it is known that MTP also plays a role in thebiosynthesis of the glycolipid presenting molecules CD1, as well as in theregulation of cholesterol ester biosynthesis. Interestingly, we recently foundthat hepatic MTP protein expression is overexpressed in several models ofmurine liver cancer. Using lomitapide, a direct inhibitor for MTP, both invitro and in vivo, we evaluated the plausible role of MTP in cancerdevelopment. We found that MTP inhibition by lomitapide strongly affects lipidmetabolism and cellular proliferation in vitro. While in vivo, lomitapide notonly affects lipid metabolism, but it also affects proliferation, apoptosis andsurvival pathways that ultimately affects tumor growth. The studies shown heredemonstrate MTP may be participating in tumor growth, and represent the firststeps in the evaluation of the role of MTP in cancer development. To discusswhether this “new” MTP role is beneficial or detrimental for tumor growth isthe aim of this presentation.