Dr. Qiao Wu is a Professor of State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University.

Abstact:
Melanoma is the most aggressive form of skin cancer with notorious resistance to apoptosis, which is a major barrier to the successful melanoma treatment. It is of great importance to identify alternative therapeutic strategies to treat melanoma other than resorting to the apoptotic induction. Autophagy, a process known to provide a survival advantage to cells during nutrient deprivation or other stresses, has also been linked to cell death, yet the associated mechanisms are largely undercharacterized. Herein it is discovered that melanoma can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to the cellular demise is launched by a specific chemical compound 1-(3,4,5-trihydroxyphenyl)- nonan-1-one (THPN), newly acquired from screening an in house library of TR3-targeting compounds. The autophagic cascade is comprised of TR3 translocation to mitochondria by interacting with the mitochondrial outer membrane protein Nix, crossing into mitochondrial inner membrane through Tom40/Tom70 channel proteins; dissipation of mitochondrial membrane potential by a permeability transition pore complex ANT1/VDAC1, and induction of autophagy. This autophagic process leads to excessive mitochondria clearance and irreversible cell death. It implicates a novel approach to melanoma therapy by activating a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death.