title: 14-3-3ζ promotes lung cancer cell invasion by increasing the Snail protein expression through atypical protein kinase C (aPKC)/NF-κB signaling.
abstract: 14-3-3ζ has been identified as a putative oncogene in several cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms underlying its functions remain undefined. In this study, we show that overexpression of 14-3-3ζ was frequently detected in lung adenocarcinoma (LuAC) tissues and was significantly associated with lymph node metastasis and poor outcome. Functional studies demonstrated that 14-3-3ζ promoted migration and invasion in A549 cells, both of which were effectively inhibited when 14-3-3ζ was silenced with short hairpin RNA (shRNA). Furthermore, 14-3-3ζ-mediated invasion of cancer cells was found to upregulate Snail through the activation of atypical protein kinase C (aPKC). Activation of aPKCζ mediates this effect by stimulating NF-κB signaling. Our results identify a specific pathway by which 14-3-3ζ induces tumor invasion and provide insight into potential therapeutic approaches to target 14-3-3ζ-associated lung adenocarcinoma.
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Song
authors.initials: S
authors.lastname: Tong
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Fan
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhai
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wangjianjununion@126.com.
authors.forename: Si-Hua
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 23024400@qq.com.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000072283:A549 Cells; D000230:Adenocarcinoma; D000077192:Adenocarcinoma of Lung; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; C572235:YWHAZ protein, human; C115015:PKC-3 protein; D011493:Protein Kinase C
keywords: 14–3-3ζ; NSCLC; Snail; aPKC