What is it about?
We report in the paper that DDA kills melanoma and leukemia cancer cells by lethal autophagy in vitro and in vivo. We further indentified the nuclear receptor LXRbeta as the DDA receptor that controls DDA cytotoxycity. We established that DDA stimulates the expression of NR4A1 (nur77), NR4A2 (NOR1), LC3A and TFEB that control lethal autophagy via LXRbeta
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Why is it important?
DDA is a newly identified cholesterol metabolite that displays tumor suppressing properties. DDA defines a new structural class of endogenous LXR ligand which metabolism is deregulated in some cancers. DDA induces an original mechanism of cell death which could complete the arsenal of molecule used for the targeted therapy of cancers.
Perspectives
We will take advantage of the induction by DDA of lethal autophagy in cancer cells to test combination therapies with conventional cytotoxic drugs to determine if DDA can sensitize cancer cells to chemotherapy.
Dr Marc Etienne Poirot
Cancer Research Center of Toulouse UMR 1037 Inserm-university of Toulouse, France
Read the Original
This page is a summary of: Dendrogenin A drives LXR to trigger lethal autophagy in cancers, Nature Communications, December 2017, Nature,
DOI: 10.1038/s41467-017-01948-9.
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