title: TAB3 overexpression promotes cell proliferation in non-small cell lung cancer and mediates chemoresistance to CDDP in A549 cells via the NF-κB pathway.
abstract: Transforming growth factor-activated kinase 1 (TAK1)-binding protein 3 (TAB3) is essential for the activation of the nuclear factor kappa B (NF-κB) pathway and has important roles in cell survival. However, the contribution of TAB3 to non-small cell lung cancer (NSCLC) remains elusive. In the present study, Western blotting and immunohistochemistry assays demonstrated that TAB3 expression was frequently increased in NSCLC tissues and cells. In addition, chi-square test and Kaplan-Meier analysis revealed that upregulation of TAB3 expression correlated with a more invasive tumor phenotype and poor prognosis. In addition, a series of experiments, including serum starvation-refeeding experiment and TAB3-siRNA transfection assay, showed that TAB3 expression promoted NSCLC cell proliferation. Furthermore, the effect of TAB3 expression on the sensitivity to cis-diamminedichloroplatinum (CDDP) and possible signaling transduction pathways was investigated. When the expression of TAB3 was inhibited by siRNA transfection, the sensitivity to CDDP was enhanced. Moreover, it showed that downregulation of TAB3 enhanced CDDP-induced A549 cell apoptosis through the inhibition of the NF-κB pathway. These results suggest that TAB3 plays a critical role in NSCLC progression and chemoresistance and that TAB3 depletion may be a promising approach to lung cancer therapy.
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China.|Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Respiratory, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ni
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. maoguoxinnt@126.com.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Mao
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China. liliji79@126.com.|Department of Pathology, Medical School of Nantong University, Nantong, 226001, China. liliji79@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D011379:Prognosis; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C481053:TAB3 protein, human; D002945:Cisplatin
keywords: Chemoresistance; NF-κB pathway; Non-small cell lung cancer; Proliferation; TAB3