title: CDC42-interacting protein 4 promotes metastasis of nasopharyngeal carcinoma by mediating invadopodia formation and activating EGFR signaling.
abstract: Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. In this study, we investigated the functional and molecular mechanisms by which CDC42-interacting protein 4 (CIP4) influences NPC.
  
  
  
  The expression levels of CIP4 were examined by Western blot, qRT-PCR or IHC. MTT assay was used to detect the proliferative rate of NPC cells. The invasive abilities were examined by matrigel and transwell assay. The metastatic abilities of NPC cells were revealed in BALB/c nude mice.
  
  
  
  We report that CIP4 is required for NPC cell motility and invasion. CIP4 promotes the activation of N-WASP that controls invadopodia formation and activates EGFR signaling, which induces downstream MMP2 (matrix metalloproteinase 2) upregulation. In addition, CIP4 could promote NPC metastasis by activating the EGFR pathway. In nude mouse models, distant metastasis was significantly inhibited in CIP4-silenced groups. High CIP4 expression is an independent adverse prognostic factor of overall survival (OS) and distant metastasis-free survival (DMFS).
  
  
  
  We identify the critical role of CIP4 in metastasis of NPC which suggest that CIP4 may be a potential therapeutic target of NPC patients.
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Radiotherapy Department, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, 510095, China.
authors.forename: Meng-Yao
authors.initials: MY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Qiang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Zi-Meng
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.|Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
authors.forename: Bi-Jun
authors.initials: BJ
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. qiancn@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. qiancn@sysucc.org.cn.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D000069261:Podosomes / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D016019:Survival Analysis; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C406285:TRIP10 protein, human; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: CIP4; EGFR/ERK/MMP-2 axis; Extracellular matrix degradation; Invadopodia formation; N-WASP; NPC