title: MACC1 down-regulation inhibits proliferation and tumourigenicity of nasopharyngeal carcinoma cells through Akt/β-catenin signaling pathway.
abstract: The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.
authors.affiliation: Department of Pathology, the First Affiliated Hospital and Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Meng
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Huijuan
authors.initials: H
authors.lastname: Shi
authors.forename: Qingxu
authors.initials: Q
authors.lastname: Yang
authors.forename: Fenfen
authors.initials: F
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Lili
authors.initials: L
authors.lastname: Kang
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhen
authors.forename: Sujuan
authors.initials: S
authors.lastname: Dai
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.forename: Anjia
authors.initials: A
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002648:Child; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: C544162:MACC1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt