We are analyzing https://link.springer.com/article/10.1007/s00280-008-0902-8.

Title:
Activation of ER stress and inhibition of EGFR N-glycosylation by tunicamycin enhances susceptibility of human non-small cell lung cancer cells to erlotinib | Cancer Chemotherapy and Pharmacology
Description:
Purpose The epidermal growth factor receptor (EGFR), an N-glycosylated transmembrane protein, is the target of erlotinib, an orally bioavailable agent approved for treatment of patients with non-small cell lung cancer (NSCLC). In this study, we examined whether inhibition of EGFR N-glycosylation and stimulation of endoplasmic reticulum (ER) stress by tunicamycin enhances erlotinib-induced growth inhibition in NSCLC cell lines. Methods We examined the effects of tunicamycin and erlotinib on cytotoxicity of erlotinib-sensitive and resistant NSCLC cell lines, as well its effects on apoptotic pathways and on EGFR activation and subcellular localization. Results A minimally cytotoxic concentration of tunicamycin (1 μM) resulted in~2.6–2.9 fold and~6.8–13.5 fold increase in erlotinib-induced antiproliferative effects in sensitive (H322 and H358) and resistant cell lines (A549 and H1650), respectively. We found that tunicamycin generated an aglycosylated form of 130 kDa EGFR. Tunicamycin additionally affected EGFR activation and subcellular localization. Interestingly, the combination of tunicamycin and erlotinib caused more inhibitory effect on EGFR phosphorylation than that of erlotinib alone. Moreover, the combination induced apoptosis in H1650 cells through induction of CHOP expression, activation of caspase-12 and caspase-3, cleavage of PARP and bak, and down-regulation of anti-apoptotic proteins bcl-xL and survivin. Conclusions Overall, our data demonstrate that tunicamycin significantly enhances the susceptibility of lung cancer cells to erlotinib, particularly sensitizing resistant cell lines to erlotinib, and that such sensitization may be associated with activation of the ER stress pathway and with inhibition of EGFR N-glycosylation.
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Keywords {🔍}

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Topics {✒️}

anti-apoptotic proteins bcl-xl month download article/chapter missak haigentz jr small-cell lung cancer er stress-induced apoptosis tunicamycin-induced er stress n-glycosylated transmembrane protein related subjects n-linked oligosaccharide chains erlotinib-induced antiproliferative effects article cancer chemotherapy lung cancer cells nsclc cell lines egfr-tki rechallenge lung cancer er full article pdf tunicamycin significantly enhances tunicamycin enhances sensitivity combination induced apoptosis resistant cell lines tunicamycin enhances susceptibility privacy choices/manage cookies er stress pathway receptor glycosylation pathways programmed cell death enhanced cytotoxicity induced sh-sy5y cells cell cycle arrest n-linked glycosylation egfr n-glycosylation growth factor phase iii trial article ling tyrosine phosphorylation sk-n-sh european economic area minimally cytotoxic concentration check access heterologous signaling systems endogenous akt/iaps mek1/erk pathways mevalonate pathway inhibits mevalonic acid depletion albert einstein college health grants ca91784 instant access lung cancer perez-soler conditions privacy policy vascular endothelial cadherin

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