{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cao X"],"funding":["National Basic Research Program of China","Priority Academic Program Development of Jiangsu Higher Education Institutions (PADD), China","National Nature Science Foundation of China","NCI NIH HHS","Natural Science Foundation of Jiangsu Province, China"],"pagination":["84-96"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6010362"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["424"],"pubmed_abstract":["Non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations initially respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and have shown favorable outcomes. However, acquired drug resistance to EGFR-TKIs develops in almost all patients mainly due to the EGFR T790 M mutation. Here, we show that treatment with low-dose EGFR-TKI results in the emergence of the EGFR T790 M mutation and in the reduction of HSP70 protein levels in HCC827 cells. Erlotinib treatment inhibits HSP70 phosphorylation at tyrosine 41 and increases HSP70 ubiquitination, resulting in HSP70 degradation. We show that EGFR-TKI treatment causes increased DNA damage and enhanced gene mutation rates, which are secondary to the EGFR-TKI-induced reduction of HSP70 protein. Importantly, HSP70 overexpression "],"journal":["Cancer letters"],"pubmed_title":["EGFR-TKI-induced HSP70 degradation and BER suppression facilitate the occurrence of the EGFR T790 M resistant mutation in lung cancer cells."],"pmcid":["PMC6010362"],"funding_grant_id":["2013CB911600","R01 CA073764","81671565","31571166","31500628","BK20161555","81471557"],"pubmed_authors":["Bi X","Xu M","Guo Z","Shen B","Zhou Y","Zhao Z","Yin Z","Cao X","Hong Z","Luo L","Lan L","Sun H","Wan F"],"additional_accession":[]},"is_claimable":false,"name":"EGFR-TKI-induced HSP70 degradation and BER suppression facilitate the occurrence of the EGFR T790 M resistant mutation in lung cancer cells.","description":"Non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations initially respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and have shown favorable outcomes. However, acquired drug resistance to EGFR-TKIs develops in almost all patients mainly due to the EGFR T790 M mutation. Here, we show that treatment with low-dose EGFR-TKI results in the emergence of the EGFR T790 M mutation and in the reduction of HSP70 protein levels in HCC827 cells. Erlotinib treatment inhibits HSP70 phosphorylation at tyrosine 41 and increases HSP70 ubiquitination, resulting in HSP70 degradation. We show that EGFR-TKI treatment causes increased DNA damage and enhanced gene mutation rates, which are secondary to the EGFR-TKI-induced reduction of HSP70 protein. Importantly, HSP70 overexpression ","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Jun","modification":"2025-04-04T09:53:59.412Z","creation":"2019-07-24T07:21:35Z"},"accession":"S-EPMC6010362","cross_references":{"pubmed":["29524558"],"doi":["10.1016/j.canlet.2018.03.004"]}}