Nuclear factor-erythroid 2-related factor 3 (NRF3) is low expressed in colorectal cancer and its down-regulation promotes colorectal cancer malignance through activating EGFR and p38/MAPK.
作者： Zigang Dong , Shan Zhou , Shan Zhou , Yuejin Li , Zhenlin Zhang
DOI:
关键词: Carcinogenesis 、 Apoptosis 、 Activating transcription factor 、 Protein kinase B 、 Epidermal growth factor receptor 、 Cancer research 、 Cell 、 Transcription factor 、 Cell growth 、 Chemistry
摘要: Nuclear factor-erythroid 2-related factor 3 (NRF3), a nuclear transcription factor, has been implicated in various cellular processes including carcinogenesis. However, mechanisms underlying its regulation carcinogenesis are unclear. Herein, we found that NRF3 is lowly expressed colorectal cancer (CRC) tissues and cells, low-expressions CRC tissue samples associated with poor patient outcomes. Nrf3-knockdown increased cell growth, colony formation, motility invasion, Nrf3-knockin dramatically decreased growth formation. Mechanistically, apoptosis arrested G2/M stage. was to be reversely epidermal receptor (EGFR) p38. Strikingly, phosphorylated-EGFR at Tyrosine845 (pEGFR Tyr845) phosphorylated-p38 Threonine180/Tyrosine182 (p-p38 Thr180/Tyr182) expressions, pEGFR Tyr845 p-p38 Thr180/Tyr182. Moreover, regulated EGFR p38 down-stream molecules, protein kinase B (AKT), activating (ATF) 2, C/EBP homologous (CHOP) expressions. loss-increased through confirmed nude mice. Collectively, NRF3-loss increases phosphorylation activation, enhances proliferation decreases apoptosis, finally promotes malignance.
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