A subunit of coatomer protein complex offers a novel tumor-specific target through a surprising mechanism.
COPI, a coatomer protein complex of secretory vesicles, is involved in Golgi and endoplasmic reticulum traffic and in early endosome maturation. The loss of COPI results in the fragmentation of Golgi, accumulation of immature autophagosomes, inhibition of autophagy, and cell death. Since COPI is required by all cells, it would appear an unlikely target for cancer treatment. However, our recent function-based genomic screen unexpectedly identified a specific COPI subunit, ζ1, as a cancer-specific target. The existing cancer drugs kill only proliferating but not growth-arrested tumor cells, but the depletion of ζ1 induces cell death in both dividing and nondividing tumor cells, while sparing normal cells. The mechanism of this remarkable tumor selectivity turned out to be surprising and heretofore unprecedented.
Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
Michael
M
Shtutman
Igor B
IB
Roninson
D000818:Animals; D020756:Coatomer Protein / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D021122:Protein Subunits / Q000378:metabolism*
D020756:Coatomer Protein; D035683:MicroRNAs; D046912:Multiprotein Complexes; D021122:Protein Subunits