MACC1 promotes carcinogenesis of colorectal cancer via β-catenin signaling pathway

Abstract

Here we confirmed that metastasis-associated in colon cancer 1 (MACC1) and β-catenin expression were higher in colorectal cancer (CRC) cells and tissues than those in normal colonic epithelial cell line and adjacent non-tumour colorectal mucosa (ANM) tissues, respectively. MACC1 expression was significantly related to histological differentiation (p<0.001), UICC stage (p=0.029), T classification (p=0.017), and N classification (p=0.023). Cox regression analysis demonstrated that high MACC1/abnormal β-catenin expression was the strongest independent prognostic indicator for reduced overall survival in CRC patients. Significant positive correlation between MACC1 expression and abnormal β-catenin expression was found in CRC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, colony formation, and tumorigenesis, both in vitro and in vivo, but induced apoptosis in CRC cells. Further MACC1 over-expression increased Met, β-catenin, and its downstream genes including c-Myc, cyclin D1, and MMP9 expression, and its upstream gene phos-GSK3β (Ser9) expression. In addition, MACC1 increased vimentin and suppressed E-cadherin in HCT116 cells. Silencing of MACC1 reversed all these changes. Our results firstly suggest that MACC1 plays an important role in carcinogenesis and progression of CRC through β-catenin signaling pathway and mesenchymal-epithelial transition.

RETRACTED: Silence of MACC1 decreases cell migration and invasion in human malignant melanoma through inhibiting the EMT

“…Recently, various studies have revealed that MACC1-induced tumorigenesis is closely correlated with hepatocyte growth factor (HGF)/ c-MET signaling pathway activation (6,10) leading to enhanced cell motility, invasion and metastasis (11). Furthermore, MACC1 could increase vimentin and suppress E-cadherin in colon cancer cells, but its silencing reversed these changes (12). To our knowledge, there is no report on its role regulating cell metastasis, as well as the underlying mechanism in carcinogenesis of malignant melanoma in the literature.…”

DKK3 blocked translocation of β‐catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc‐3 cell

“…The following antibodies were used: β‐catenin, DKK3, cyclin D1, c‐Myc (Santa Cruz Biotech) 18, E‐Cadherin (Epitomics Inc.), vimentin, cleaved caspase‐3, cleaved caspase‐9, cleaved caspase‐7, cleaved PARP, E‐cadherin, vimentin, N‐Cadherin, Histone 1 (Cell Signaling Technology, Danvers, MA, USA) 19, β‐actin (Sigma‐Aldrich) 20, survivin, OCT4 and CD133 (Santa Cruz Biotech) 21, Glyceraldehyde 3‐phosphate dehydrogenase (Abcam) 22.…”

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].…”

“…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]. Recently, Wang et al [69] showed that MACC1 upregulates Twist-1/-2, a key EMT switch transcriptional regulator.…”