title: NEDD4 is involved in acquisition of epithelial-mesenchymal transition in cisplatin-resistant nasopharyngeal carcinoma cells.
abstract: Nasopharyngeal carcinoma (NPC) is a highly invasive head-neck cancer derived from the nasopharyngeal epithelium, mainly prevalent in southern China and Southeast Asia. Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard administrations applied in the treatment of NPC. However, resistance to chemotherapeutic drugs has recently become more common, resulting in worse treatment outcome for NPC therapy. To elucidate the underlying molecular basis of drug resistance to DDP in NPC cells, we examined the morphocytology, cell motility and molecular changes in DDP-resistant NPC cells with respect to epithelial-mesenchymal transition (EMT) features. We found that EMT is closely associated with DDP-induced drug resistance in NPC cells, as DDP-resistant cells displayed morphological and molecular markers changes consistent with EMT. Wound healing and Transwell Boyden chamber assays revealed an enhanced migration and invasion potential in DDP-resistant NPC cells. Mechanistically, upregulation of NEDD4 was observed to relate to EMT in DDP-resistant cells. More importantly, depletion of NEDD4 in resistant cells led to a partial reversion of EMT phenotypes to MET characteristics. These data suggest that NEDD4 is largely involved in EMT features and chemoresistance of NPC cancer cells. NEDD4 could be a novel therapeutic target to overcome drug resistance in successful administrations of NPC.
authors.affiliation: a Department of Otorhinolaryngology, Head and Neck Surgery , The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.|b Department of Otorhinolaryngology , Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai , China.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Feng
authors.affiliation: c Department of Radiation Oncology , The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai , China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Yang
authors.affiliation: d Department of Otolaryngology , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Haidi
authors.initials: H
authors.lastname: Yang
authors.affiliation: c Department of Radiation Oncology , The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai , China.
authors.forename: Zibin
authors.initials: Z
authors.lastname: Liang
authors.affiliation: e Department of Orthopaedics , The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai , China.
authors.forename: Rongkai
authors.initials: R
authors.lastname: Zhang
authors.affiliation: b Department of Otorhinolaryngology , Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai , China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Fan
authors.affiliation: a Department of Otorhinolaryngology, Head and Neck Surgery , The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.
authors.forename: Gehua
authors.initials: G
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000075702:Nedd4 Ubiquitin Protein Ligases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D002945:Cisplatin
keywords: EMT; NEDD4; Nasopharyngeal carcinoma; drug resistance