Overexpression of Metastasis-Associated in Colon Cancer-1 Associated with Poor Prognosis in Patients with Esophageal Cancer

Zhu, Min; Xu, Yu; Mao, Xuelian; Gao, Yanfang; Shao, Lan; Yan, Feng

doi:10.1007/s12253-013-9638-9

Cited by 29 publications

(26 citation statements)

References 23 publications

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“…Therefore, MACC1 has been suggested as a potential biomarker for metastasis and invasion of colorectal cancer and primary hepatocellular carcinoma (16). High levels of MACC1 are also associated with lymph node metastasis and TNM stage in esophageal cancer, as well as a lower OS and a higher risk of death (17). The present study demonstrated that positive expression of MACC1 was significantly higher in GTs compared with ATs, and significantly correlated with invasion depth, TNM stage and differentiation status.…”

Section: Macc1 Overexpression Enhances Migration and Invasion In Gastsupporting

confidence: 60%

MACC1 and HGF are associated with survival in patients with gastric cancer

Dong

Wang

et al. 2017

Oncol Lett

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Abstract. Metastasis-associsated in colon cancer 1 (MACC1), a newly identified oncogene, promotes tumor cell proliferation and invasion. In the present study, the expression of MACC1, hepatocyte growth factor (HGF) and its receptor, MET proto-oncogene (c-Met), was investigated in human gastric cancer tissues and adjacent normal tissues by immunohistochemistry. The association between the expression levels of the proteins and the clinicopathological parameters of the tumors were statistically analyzed. Furthermore, lentiviral particles expressing MACC1 were used to infect the hepatic satellite cell (HSC) line LX2. The expression of α-smooth muscle actin (SMA), HGF, matrix metallopeptidase (MMP)-2 and MMP-9 in human HSCs was examined by western blotting and reverse transcription-quantitative polymerase chain reaction. Transwell assays were used to measure the effect of MACC1-infected or non-infected HSCs on the migration and invasion abilities of MKN45 and MKN74 gastric carcinoma cells in vitro. The results demonstrated that positive protein expression of MACC1, HGF and c-Met was significantly higher in human gastric cancer tissues compared with adjacent normal tissues. Positive expression of MACC1 and c-Met in gastric cancer tissues had no correlation with the sex, age, tumor location and peritoneal metastasis of patients, but was significantly correlated with tumor size, depth of tumor invasion, lymph node metastasis, TNM stage, histological differentiation, and overall (5 years) and disease-free survival (5 years). Positive expression of each MACC1, HGF and c-Met protein was demonstrated to be positively correlated with each other in human gastric cancer tissues. Western blotting results confirmed that MACC1 protein was overexpressed in MACC1-overexpressing lentivirus-infected HSCs. Overexpression of MACC1 significantly increased HGF, MMP-2, MMP-9 and α-SMA expression levels in HSCs. Results from the Transwell assays indicated an increase in the number of MKN45 or MKN74 cells migrating towards MACC1-overexpressing HSCs, compared with control HSCs. These findings suggested that MACC1 may regulate the expression of HGF, MMP-2 and MMP-9 in HSCs, and may thus promote migration and invasion of gastric carcinoma cells. MACC1, HGF and c-Met might cooperatively participate in the malignant progression of gastric cancer. In conclusion, MACC1 might serve as a useful molecular target for the diagnosis, treatment and prognosis of gastric cancer.

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Section: Macc1 Overexpression Enhances Migration and Invasion In Gastsupporting

confidence: 60%

MACC1 and HGF are associated with survival in patients with gastric cancer

Dong

Wang

et al. 2017

Oncol Lett

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“…Metastasis-associated in colon cancer-1(MACC1), a newly identified key regulator of hepatocyte growth factor (HGF)-MET signaling, predicts colon cancer metastasis [1-3]. Recently, MACC1 expression has been found in lung cancer [4], hepatocellular carcinoma [5], ovarian carcinoma [6], gastric carcinoma [7], esophageal cancer [8], and nasopharygneal carcinoma [9]. Overexpression of MACC1 associates with the progression of these carcinomas and prognosis of the patients with these carcinomas [4, 7, 8].…”

Section: Introductionmentioning

confidence: 99%

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

Zhen

Dai²,

Li³

et al. 2014

Oncotarget

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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.

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“…MACC1, first identified as a colon cancer oncogene, potentially functions as an early diagnosis biomarker and is associated with the progression of multiple solid tumors (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Stein et al (12) demonstrated that MACC1 upregulation was associated with benign-malignant tumor transition.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, previous studies have revealed that the abnormal expression of MACC1 may be associated with the development and progression of numerous types of solid tumor, including lung (13,14) and gastric cancer (15)(16)(17)(18), hepatocellular carcinoma (19)(20)(21), breast cancer (22), glioma (23) and colon (12,24) and esophageal cancer (25). These studies suggested that MACC1 may serve as a key biomarker for recurrence, metastasis and patient survival in multiple types of human cancer.…”

Section: Introductionmentioning

confidence: 94%

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

Qian

Xia-qin²,

et al. 2017

Oncology Letters

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Abstract.As an oncogene, MACC1 serves an important function in cancer progression and metastasis. However, the effect of MACC1 in esophageal carcinoma (EC) remains to be fully understood. The present study assessed the association between MACC1 expression and the progression of EC cells. A small interfering (si)RNA was delivered into EC cells to downregulate MACC1 expression. The MTT assay demonstrated that EC cell viability was reduced by siRNA-MACC1. Decreasing MACC1 expression increased the apoptotic rate of EC cells compared with control cells. Transwell and Matrigel assays demonstrated that EC cell migration and invasion, respectively, were downregulated by siRNA-MACC1. Furthermore, knocking down MACC1 suppressed the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by upregulating the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor. The results of the present study revealed that MACC1 expression affected cellular functions of the EC cells through the PTEN/PI3K/Akt signaling pathway. Therefore, MACC1 may potentially serve as a novel biomarker and therapeutic target for EC.

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Overexpression of Metastasis-Associated in Colon Cancer-1 Associated with Poor Prognosis in Patients with Esophageal Cancer

Cited by 29 publications

References 23 publications

MACC1 and HGF are associated with survival in patients with gastric cancer

MACC1 and HGF are associated with survival in patients with gastric cancer

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

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

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