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.
Highlights
Nasopharyngeal carcinoma (NPC) is relatively rare in the Western world, but more common in Southern China and Southeast Asia, with an annual incidence rate of about 20 per 100,000 people in endemic areas[1]
We found that metastasis-associated in colon cancer 1 (MACC1) expression was much higher in Epstein- Barr virus (EBV)-positive NPC cell line C666-1 than other EBV-negative NPC cell lines (Figure 1A)
MACC1 mRNA expression was dramatically higher in EBV-positive NPC cell line C666-1 than other EBV-negative NPC cell lines (Figure 1B)
Summary
Nasopharyngeal carcinoma (NPC) is relatively rare in the Western world, but more common in Southern China and Southeast Asia, with an annual incidence rate of about 20 per 100,000 people in endemic areas[1]. EBV-encoded oncogene latent membrane protein 1 (LMP1) is an important oncogene, which is involved in the activation of signal transduction pathways, such as the nuclear factor-kB, signal transducer and activator of transcription, and activator protein 1, which mediates various biological functions including proliferation, apoptosis, differentiation, and metastasis[3]. The Wnt/b-catenin signaling pathway is tightly regulated and has important functions in development, tissue homeostasis, and regeneration. Oncogenic activation of the Wnt/b-catenin signaling pathway by mutation in adenomatous polyposis coli or bcatenin, which results in the cytoplasmic and nuclear b-catenin accumulation and in b-catenin/T-cell factor (TCF) 4—regulated transcription of TCF target genes such as cyclin D1 and c-Myc, is mandatory for the initial neoplastic transformation of intestinal epithelium[4]. Our previous study has reported that LMP1 increases nuclear b-catenin accumulation and its transcriptional activity in NPC[5]. Our previous study has reported that LMP1 increases nuclear b-catenin accumulation and its transcriptional activity in NPC[5]. b-catenin knockdown dramatically inhibited cellular growth, migration and invasion, but induced apoptosis of NPC cells[6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
