The discovery that the lipid C18-ceramide is a tumor suppressor provides insight into the autophagy paradox, as reported online in Nature Chemical Biology this week. This work may open new avenues for the development of anti-cancer therapies.
There are many ways that a cell can die, including through a process termed autophagy. Paradoxically under different conditions, autophagy can promote either cell survival or cell death. The events that control these disparate cellular outcomes have, until now, remained elusive.
Besim Ogretmen and colleagues report that C18-ceramide, a lipid and a putative tumor suppressor, interacts with a protein called LC3B-II and tethers it to the membrane of a cellular organelle, known as the mitochondrion. They also show that persistent localization of LC3B-II in the mitochondrial membrane leads to mitochondrial dysfunction and ultimately cell death. In addition they noted that overproduction of C18-ceramide was sufficient to slow the growth of xenografted tumors in mice.
Collectively, these data provide evidence that C18-ceramide has tumor suppressor activity and opens a new avenue for the identification of anti-cancer agents.
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