title: Down-regulation of prostate stem cell antigen (PSCA) by Slug promotes metastasis in nasopharyngeal carcinoma.
abstract: Distant metastasis and local recurrence are still the major causes for failure of treatment in patients with nasopharyngeal carcinoma (NPC), making it urgent to further elicit the molecular mechanisms of NPC metastasis. Using a gene microarray including transcription factors and known markers for cancer stem cells, prostate stem cell antigen (PSCA) was found to be significantly down-regulated in metastatic NPC in lymph node, compared to its primary tumour, and in NPC cell lines with high metastatic ability compared to those with low metastatic ability. NPC patients with low PSCA expression had a consistently poor metastasis-free survival (p = 0.003). Knockdown and overexpression of PSCA respectively enhanced and impaired the migration and invasion in vitro and the lung metastasis in vivo of NPC cells. Mechanistically, the enhancement of NPC metastasis by knocking down PSCA probably involved epithelial-mesenchymal transition (EMT), by up-regulating N-cadherin and ZEB1/2 and by activating RhoA. The down-regulation of PSCA in NPC cells resulted directly from the binding of Slug to the PSCA promoter. PSCA may be a potential diagnostic marker and therapeutic target for patients with NPC.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.|Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, The Third Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Ru-Hua
authors.initials: RH
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Luo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Wu-Guo
authors.initials: WG
authors.lastname: Deng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Tiebang
authors.initials: T
authors.lastname: Kang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: N-cadherin; PSCA; RhoA; Slug; ZEB1; ZEB2; epithelial-to-mesenchymal transition; nasopharyngeal carcinoma