biostudies-literatureZolekar ANIA NIH HHS1538-1551https://www.ebi.ac.uk/biostudies/studies/S-EPMC6288164biostudies-literatureUnknown119(12)<h4>Background</h4>Although NGLY1 is known as a pivotal enzyme that catalyses the deglycosylation of denatured glycoproteins, information regarding the responses of human cancer and normal cells to NGLY1 suppression is limited.<h4>Methods</h4>We examined how NGLY1 expression affects viability, tumour growth, and responses to therapeutic agents in melanoma cells and an animal model. Molecular mechanisms contributing to NGLY1 suppression-induced anticancer responses were revealed by systems biology and chemical biology studies. Using computational and medicinal chemistry-assisted approaches, we established novel NGLY1-inhibitory small molecules.<h4>Results</h4>Compared with normal cells, NGLY1 was upregulated in melanoma cell lines and patient tumours. NGLY1 knockdown caused melanoma cell deBritish journal of cancerStress and interferon signalling-mediated apoptosis contributes to pleiotropic anticancer responses induced by targeting NGLY1.PMC6288164T32 AG020494Ho YYSampat RZolekar ALiu JLin VJTEmmitte KAHayatshahi HSLiao XWang YCMishra NMHoffmann PParab AfalseStress and interferon signalling-mediated apoptosis contributes to pleiotropic anticancer responses induced by targeting NGLY1.<h4>Background</h4>Although NGLY1 is known as a pivotal enzyme that catalyses the deglycosylation of denatured glycoproteins, information regarding the responses of human cancer and normal cells to NGLY1 suppression is limited.<h4>Methods</h4>We examined how NGLY1 expression affects viability, tumour growth, and responses to therapeutic agents in melanoma cells and an animal model. Molecular mechanisms contributing to NGLY1 suppression-induced anticancer responses were revealed by systems biology and chemical biology studies. Using computational and medicinal chemistry-assisted approaches, we established novel NGLY1-inhibitory small molecules.<h4>Results</h4>Compared with normal cells, NGLY1 was upregulated in melanoma cell lines and patient tumours. NGLY1 knockdown caused melanoma cell de2018-01-01T00:00:00Z2018 Dec2026-05-05T22:16:28.204Z2019-07-25T07:11:38ZS-EPMC62881643038582210.1038/s41416-018-0265-9