Palmitoylated SCP1 is targeted to the plasma membrane and negatively regulates angiogenesis

Cancerous tumors are the leading cause of death worldwide. Tumors cannot grow beyond a couple of millimeters in diameter unless they are supplied with nutrients and oxygen. To receive these, tumors connect to the body’s blood supply by stimulating the growth of new blood vessels. Drugs that reduce the ability of new blood vessels to form have therefore been investigated as possible anti-cancer treatments. New blood vessels emerge from pre-existing ones in a process called angiogenesis. The first stage of angiogenesis involves the endothelial cells that line the inner wall of the blood vessels moving outwards to form new ‘sprouts’. Within the endothelial cells, a signaling protein called AKT drives angiogenesis by moving to the cell membrane, where it is activated and triggers further signaling events. The activation of AKT occurs via a phosphate group being attached to a particular site on the protein. Enzymes called phosphatases remove phosphate groups from proteins and so can inactivate AKT, hence preventing angiogenesis. Although some phosphatases are known to inactivate AKT, they cannot easily be counted or analyzed. This means that they cannot be used to develop new cancer treatments. In addition, for the phosphatase to best prevent tumor growth, it should inactivate AKT at the cell membrane. Liao, Wang, Li, Wang, Jin et al. now show that a phosphatase called SCP1 can localize to the cell membrane and inactivate AKT there. SCP1 was not previously known to anchor to the cell membrane. Liao et al. found that this anchoring occurs via a modification that attaches a fatty acid molecule to SCP1. Further experiments showed that mice that lacked SCP1 had increased levels of AKT phosphorylation in their endothelial cells, more new blood vessel growth and, consequently, had tumors that grew faster. Further research is now needed to investigate exactly how SCP1 moves to the cell membrane from elsewhere in the cell. Ultimately, this knowledge could play an important role in identifying potential drugs that prevent or reduce the growth of tumors.