Significance of aeg‐1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple‐negative breast cancer

Liu, Cong; Li, Rui; Song, Haoming; Wang, Dong; Tian, Feng; Yu, Xiaoguang; Zhao, Yulan; Liu, Junjun; Yu, Xiaoyu; Wang, Yanbo; Geng, Jiao

doi:10.1002/jso.21788

Cited by 69 publications

(56 citation statements)

References 48 publications

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“…The first was its ability to interact and activate the b-catenin pathway (12); and second, the emerging evidence that MTDH/ AEG-1 may coordinate the activity of several signaling pathways all leading to the progression of tumor growth and spread in a number of different tumor types (including glioblastoma; ref. [13][14][15][16][17]. If CPEB1 is regulating the synthesis of MTDH/AEG-1, it would suggest that CPEB1 is coordinating the synthesis of proteins that are functionally related (e.g., b-catenin and MTDH/AEG-1), and that targeting CPEB1-mediated protein synthesis might be useful in many types of cancer not just glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

Kochanek

Wells

2013

Molecular Cancer Research

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Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an mRNA-binding protein present in both neurons and glia. CPEB1 is capable of both repressing mRNA translation and activating it depending upon its phosphorylation state. CPEB1-bound mRNAs are held in translational dormancy until CPEB1 is phosphorylated, leading to the cytoplasmic polyadenylation of the bound mRNA that triggers translation. Here, we show that CPEB1 can bind to and regulate translation of the mRNA-encoding metadherin (MTDH, also known as AEG-1 and Lyric) in the rat glioblastoma cell line CNS1. MTDH/AEG-1 is being revealed as a critical signaling molecule in tumor progression, playing roles in invasion, metastasis, and chemoresistance. By using a mutant of CPEB1 that cannot be phosphorylated (thereby holding target mRNAs in translational arrest), we show that inhibiting CPEB1-mediated translation blocks MTDH/AEG-1 expression in vitro and inhibits glioblastomas tumor growth in vivo. CPEB1-mediated translation is likely to impact several signaling pathways that may promote tumor progression, but we present evidence suggesting a role in directed cell migration in glioblastoma cells. In addition, reporter mRNA containing CPEB1-binding sites is transported to the leading edge of migrating cells and translated, whereas the same mRNA with point mutations in the binding sites is synthesized perinuclearly. Our findings show that CPEB1 is hyperactive in rat glioblastoma cells and is regulating an important cohort of mRNAs whose increased translation is fueling the progression of tumor proliferation and dispersal in the brain. Thus, targeting CPEB1-mediated mRNA translation might be a sound therapeutic approach. Mol Cancer Res; 11(2); 149-60. Ó2012 AACR.

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Section: Introductionmentioning

confidence: 99%

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

Kochanek

Wells

2013

Molecular Cancer Research

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“…Overexpression of MTDH has been frequently observed in a variety of primary human tumors, including breast cancer (7)(8)(9)(10), multiform glioblastoma (11)(12)(13), neuroblastoma (14,15), gastric cancer (16), colorectal carcinoma (17), osteosarcoma (18), gallbladder carcinoma (19), head and neck squamous cell carcinoma (HNSCC) (20) (26), and prostate cancer (6,27,28). Furthermore, published studies on some cancers have revealed that MTDH is a novel and useful prognostic marker for cancer progression, and its overexpression is associated with an unfavorable prognosis (7,8,13,(15)(16)(17)23,24,26,28,29). The role of MTDH in HCC has long been debated.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of metadherin overexpression in hepatitis B virus-related hepatocellular carcinoma

et al. 2012

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Abstract. Metadherin (MTDH), which is an HIV-1 or TNF-α-inducible transcript, has a crucial role in several types of cancer by regulating multiple cellular signaling processes. However, to date, the role of MTDH in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is still unclear. In the present study, we detected MTDH expression in normal liver, chronic hepatitis B and HBV-related HCC tissues. The data showed that MTDH expression levels were elevated in the hepatitis B tissues and especially in the HBV-related HCC tissues compared to normal liver tissues. There was a trend for gradually increased MTDH expression from normal liver tissue to hepatitis B and HBV-related HCC tissues. Furthermore, a statistical analysis revealed that MTDH expression significantly correlated with the American Joint Committee on Cancer (AJCC, 7th edition) stage (P=0.020), T classification (P= 0.007), N classification (P= 0.044), vascular invasion (P=0.006) and histological differentiation (P=0.020) in the HBV-related HCC patients. In addition, patients with high MTDH levels had shorter survival times compared to those with low MTDH expression (P=0.001). Taken together, these results suggest that MTDH could be a potential prognostic marker for overall survival and tumor progression and a chemotherapeutic target in HBV-related HCC patients.

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“…In addition, the previous studies have demonstrated that there were many microvessel in IMPC [29] and the VEGF-C high expression was associated with lymph node metastasis of IMPC [30] . The significance of MTDH expression was in correlation with VEGF in triple-negative breast cancer [31] . MTDH is indeed a direct regulator of angiogenesis by up-regulating key components, such as vascular endothelial growth factor (VEGF), which plays an important role in the process of blood vessel formation [32,33] .…”

Section: Discussionmentioning

confidence: 92%

MTDH expression in invasive micropapillary carcinoma of the breast

Hao

Yang

Liu

et al. 2011

Clin. Oncol. Cancer Res.

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OBJECTIVE To clarify the expression of MTDH in invasive micropapillary carcinoma of the breast (IMPC) and analyze the relationship between MTDH expression and clinicalpathologic parameters of the IMPC patietns. METHODS The expression of MTDH protein was analyzed using immunohistochemical staining in 86 cases with IMPC and another 86 cases with invasive ductal carcinoma not otherwise specified (IDC-NOS). The association between MTDH expression and clinicalpathologic parameters of the IMPC patients was analyzed. RESULTS Immunohistochemical analysis revealed the high expression of MTDH in 64 of the 86 (64/86, 74.4%) IMPC patients and in 45 of the 86 (45/86, 52.3%) IDC-NOS patients. Statistical analysis showed a statistically significant difference in MTDH expression between IMPC and IDC-NOS (P , 0.05). In IMPC, the expression of MTDH was correlated with lymph nodes metastasis (P , 0.05). The expression of MTDH was negative in normal breast tissue of IMPC and IDC-NOS patients. CONCLUSION High expression of MTDH is one of the molecular mechanisms, which facilitates lymph node metastasis of IMPC, therefore, the expression level of IMPC plays an important role in lymph node metastasis of IMPC.KEY WORDS: breast carcinoma, invasive micropapillary carcinoma, metadherin, lymph node metastases.

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Significance of aeg‐1 expression in correlation with vegf, microvessel density and clinicopathological characteristics in triple‐negative breast cancer

Abstract: AEG-1 expression may be related with tumor angiogenesis and progression and is a valuable prognostic factor in patients with triple-negative breast cancer.

Cited by 69 publications

References 48 publications

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

Prognostic significance of metadherin overexpression in hepatitis B virus-related hepatocellular carcinoma

MTDH expression in invasive micropapillary carcinoma of the breast

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