title: BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.
abstract: BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital,Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Lu
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Wendan
authors.initials: W
authors.lastname: Yu
authors.affiliation: The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Tang
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Tang
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Xiuna
authors.initials: X
authors.lastname: Sun
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.|State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.|State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors.forename: Wu-guo
authors.initials: WG
authors.lastname: Deng
authors.affiliation: The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China.
authors.forename: Taihua
authors.initials: T
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism*; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; D014157:Transcription Factors; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins
keywords: BPTF; lung cancer; prognosis; tumor growth