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It is important to exploit new potential of molecularly targeted therapies. High-frequency somatic mutations in\n                      <jats:italic>KEAP1\/NRF2<\/jats:italic>\n                      (27.9%) have been identified in lung squamous cell carcinoma. In this research, we explored the role of\n                      <jats:italic>KEAP1<\/jats:italic>\n                      somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target\u00a0lung cancer carrying\n                      <jats:italic>KEAP1\/NRF2<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Lung cancer cell lines A549 and H460 with loss-of-function mutations in\n                      <jats:italic>KEAP1<\/jats:italic>\n                      stably transfected with wild-type (WT)\n                      <jats:italic>KEAP1<\/jats:italic>\n                      or somatic mutations in\n                      <jats:italic>KEAP1<\/jats:italic>\n                      were used to investigate the functions of somatic mutations in\n                      <jats:italic>KEAP1<\/jats:italic>\n                      . Flow cytometry, plate clone formation experiments, and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression of NRF2 and its target genes increased\n                      <jats:italic>,<\/jats:italic>\n                      and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with\n                      <jats:italic>KEAP1<\/jats:italic>\n                      mutants compared to control cells with a loss-of-function\n                      <jats:italic>KEAP1<\/jats:italic>\n                      mutation and stably transfected with WT\n                      <jats:italic>KEAP1<\/jats:italic>\n                      in both in vitro and in vivo studies. The proliferation of A549 cell line trasfected with the R320Q\n                      <jats:italic>KEAP1<\/jats:italic>\n                      mutant was inhibited more apparent than that of the A549 cell line trasfected with WT\n                      <jats:italic>KEAP1<\/jats:italic>\n                      after treatment with NRF2 inhibitor ML385.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Somatic mutations of\n                      <jats:italic>KEAP1<\/jats:italic>\n                      identified from patients with LSCC likely promote tumorigenesis mediated by activation of the KEAP1\/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with\n                      <jats:italic>KEAP1<\/jats:italic>\n                      mutation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-020-00568-z","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T07:03:07Z","timestamp":1592895787000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Loss-of-function mutations in KEAP1 drive lung cancer progression via KEAP1\/NRF2 pathway activation"],"prefix":"10.1186","volume":"18","author":[{"given":"Meiling","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixia","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"issue":"1","key":"568_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21387","volume":"67","author":"RL Siegel","year":"2017","unstructured":"Siegel RL, Miller KD, Jemal A. 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