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.

Underlying Mechanisms for Distant Metastasis - Molecular Biology

“…For various cancer cell lines, MACC1 has proven to induce proliferation and inhibit apoptosis [65,66]. Furthermore, several studies have revealed MACC1 to induce EMT by increasing the mesenchymal phenotype markers vimentin and CD44 and suppressing the epithelial phenotype markers E-cadherin and α-catenin [66][67][68].…”

“…Overexpression of Oct4 and Nanog contributes to the stem cell phenotype of tumor cells [70]. MACC1 is also involved in migration, invasion, and angiogenesis [65][66][67][71][72][73]. Additionally, overexpression of MACC1 facilitates tumor blood supply by inducing vasculogenic mimicry, the formation of vascular channels in the absence of endothelial cells and fibroblasts [69].…”

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

“…It has been demonstrated that MACC-1 expression is correlated with c-Met expression in GC (79). Furthermore, silencing MACC-1 can inhibit VEGF-C/VEGF-D expression and thus inhibit lymphangiogenesis (80).…”

Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway

“…Previous studies have suggested that MACC1 is associated with the Akt and Ras/EPH receptor B2 signaling pathways (28)(29)(30). Zhang et al (28) demonstrated that MACC1 expression may affect the PI3K/Akt signaling pathway and the protein expression of matrix metallopeptidase (MMP)2 and MMP9.…”

“…Zhang et al (28) demonstrated that MACC1 expression may affect the PI3K/Akt signaling pathway and the protein expression of matrix metallopeptidase (MMP)2 and MMP9. Meng et al (30) revealed that pAkt was a key target gene of MACC1, and that pAkt expression was significantly suppressed by MACC1 downregulation in nasopharyngeal carcinoma cells. In the present study, downregulating MACC1 expression increased the expression of PTEN and decreased the phosphorylation of Akt in EC cells.…”