title: High FMNL3 expression promotes nasopharyngeal carcinoma cell metastasis: role in TGF-β1-induced epithelia-to-mesenchymal transition.
abstract: Formin-like 3 (FMNL3) plays a crucial role in cytoskeletal mediation and is potentially a biomarker for cell migration; however, its role in cancer metastasis remains unknown. In this study, we found elevated FMNL3 protein expression in clinical nasopharyngeal carcinoma (NPC) tissues. FMNL3 expression positively correlated to the clinical stage, T (tumour), N (lymph node metastasis) and M (distant metastasis) classification of NPC patients. Moreover, FMNL3 positively correlated to Vimentin expression and negatively correlated to E-cadherin expression in clinical NPC samples. In vitro experiments showed that FMNL3 expression was inversely related to NPC cell differentiation status. Overexpression of FMNL3 led to epithelial-to-mesenchymal transition (EMT) in well differentiated CNE1 cells. TGF-β1-treated poorly differentiated CNE2 cells showed changes in EMT accompanied by enhanced FMNL3 expression and cell migration. On the contrary, knockdown of FMNL3 partially attenuated the TGF-β1-promoted CNE2 cell migration, together with associated changes in EMT markers. Finally, knockdown of FMNL3 also weakened EMT in tumours in xenographs. Our study indicates for the first time that TGF-β1/FMNL3 signalling may be a novel mechanism mediating EMT in NPC, which is closely associated with NPC metastasis.
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Keke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Ha
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Pathophysiology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.|Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Ding
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Gan
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Rujia
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Botao
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Hanguo
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Guangdong Medical University, Zhanjiang 524023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jie
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D000080865:Formins; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; C476209:FMNL3 protein, human; D000080865:Formins; D011506:Proteins; D053773:Transforming Growth Factor beta1; D014746:Vimentin