title: Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer.
abstract: Acquired resistance to standard chemotherapy causes treatment failure in patients with local advanced and advanced non-small lung cancer (NSCLC). Cancer stem cells (CSCs) are a small subpopulation within cancer that is thought to be resistant to conventional chemotherapy. The Notch pathway is one of the most intensively studied for putative therapeutic targets of CSCs in solid tumors. In our study, suppression of Notch3 decreased colony and sphere formation of stem-like property in lung cancer cells. In addition, Notch3 expression was demonstrated to be upregulated in the patients with chemoresistance and related to poor prognosis of NSCLC patients. Our results also showed that CSC markers ALDH1A1 and CD44 were highly expressed in NSCLC patients with chemoresistance and these two markers were positively correlated with Notch3 expression in lung cancer specimens from TCGA database. Furthermore, the lung cancer cells with drug resistance were shown to be associated with activation of autophagy. All the data support a crucial role of Notch3 in the increase of stem-like property in NSCLC cells that might be associated with upregulation of ALDH1A1 and CD44 and activation of autophagy.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Beijing Center for Physical and Chemical Analysis, Beijing 100089, P.R. China.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Si
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Fangliang
authors.initials: F
authors.lastname: Lu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Liyi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis*; D000080924:Aldehyde Dehydrogenase 1 Family; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D001343:Autophagy / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D000071656:Receptor, Notch3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050697:Retinal Dehydrogenase
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D053829:Amyloid Precursor Protein Secretases; D002945:Cisplatin