title: TFAP2C-mediated upregulation of TGFBR1 promotes lung tumorigenesis and epithelial-mesenchymal transition.
abstract: TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression. TGFBR1 upregulation induced by TFAP2C also promoted cell motility and migration, leading to malignant development. We also found that PAK1 (p21 protein (Cdc42/Rac)-activated kinase 1) signaling was involved in TFAP2C/TGFBR1-induced tumorigenesis. These results were confirmed by an in vivo xenograft model and patient tissue samples. This study shows that TFAP2C promoted tumor progression by upregulation of TGFBR1 and consequent activation of PAK1 signaling.
authors.affiliation: Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.|Integrative Graduate Program of Ship and Offshore Plant Technology for Ocean Energy Resource, Pusan National University, Busan, Republic of Korea.
authors.forename: Wanyeon
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
authors.forename: EunGi
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
authors.forename: Sungmin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
authors.forename: Daehoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
authors.forename: Jahyun
authors.initials: J
authors.lastname: Chun
authors.affiliation: Department of Chemistry, Pusan National University, Busan, Republic of Korea.
authors.forename: Kang Hyun
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
authors.forename: HyeSook
authors.initials: H
authors.lastname: Youn
authors.affiliation: Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.|Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
authors.forename: BuHyun
authors.initials: B
authors.lastname: Youn
mesh_terms: D000368:Aged; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D018125:Receptors, Transforming Growth Factor beta; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse