Drug Resistance Mediated by AEG-1/MTDH/LYRIC

Meng, Xiangjun; Thiel, Kristina W.; Leslie, Kimberly K.

doi:10.1016/b978-0-12-401676-7.00005-x

Cited by 56 publications

(70 citation statements)

References 81 publications

(136 reference statements)

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“…Downregulation of N-cadherin and snail, upregulation of E-cadherin, and translocation of β-catenin by depletion expression of MTDH in HCC cell lines indicates that MTDH may promote HCC metastasis through the induction of the epithelialmesenchymal transition (EMT) process [47,48]. Moreover, MTDH overexpression was correlated with clinicopathologic characters including cell proliferation, invasion, metastasis, chemoresistance, angiogenesis and poor clinical outcome [40,49,50]. A gradual increase in MTDH expression in normal liver tissue to hepatitis B and HBV-related HCC tissue levels was observed [51].…”

Section: Mechanisms Of Mtdh Overexpression In Hccmentioning

confidence: 95%

“…MTDH might function as a RNA binding protein to regulate the levels of important DNA repair factors at the post-transcriptional level. Previous work has shown that MTDH can promote translation of the multiple drug resistance gene MDR1 and the angiogenesis gene factor XII (FXII) [36,39,40]. Therefore, targeting MTDH might impair the ability of cancer cells to rapidly repair their DNA and increase therapeutic efficacy.…”

Section: Role Of Mtdh As An Rna Binding Protein In Drug Resistancementioning

confidence: 99%

“…HCC in both wild-type mice or in Arf(−/−)Rosa26-FOXM1 Tg mice was induced by diethylnitrosamine/phenobarbital. These HCC-bearing mice were then injected daily with the cell-penetrating ARF (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) peptide inhibitor to pharmacologically reduce FOXM1 activity. After 4 weeks of this treatment, HCC regions displayed reduced tumor cell proliferation and angiogenesis within the HCC region but not in the adjacent normal liver tissue.…”

Section: Foxm1 Acts As a Therapeutic Target Of Hccmentioning

confidence: 99%

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Role of MTDH, FOXM1 and microRNAs in Drug Resistance in Hepatocellular Carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is one of the most lethal malignancies due to underlying co-morbid cirrhosis and chemo-resistance. Vaccination and improved treatment for hepatitis are the most effective means to reduce the burden of liver cancer worldwide. Expression of biomarkers such as AFP (alpha-fetoprotein), DDK1 (Dickkopf WNT Signaling Pathway Inhibitor 1) and microRNAs in blood are being tested for early screening of liver cancer. Since 2008, sorafenib has been used as the standard molecular targeting agent for HCC. However, overall outcomes for sorafenib alone or in combination with other tyrosine kinase inhibitors are unsatisfactory. Whether simultaneously or sequentially, addiction switches and compensatory pathway activation in HCC, induced by sorafenib treatment, may induce acquired resistance. Forkhead box M1 (FOXM1) and metadherin (MTDH) have been shown to be master regulators of different aspects of tumorigenesis, including angiogenesis, invasion, metastasis and drug resistance. Elevated expression of both FOXM1 and MTDH is known to be a consequence of both activating mutations in oncogenes such as PI3K, Ras, myc and loss of function mutations in tumor suppressor genes such as p53 and PTEN in various types of cancers including HCC. The role of FOXM1 and MTDH as potential prognostic markers as well as therapeutic targets in HCC will be discussed. In addition, microRNAs (miRNAs), endogenous small noncoding RNAs involved in the regulation of gene expression, are involved in HCC and interact with both FOXM1 and MTDH in several ways. Thus, altered expression of miRNAs in HCCs will also be discussed as potential tools for diagnosis, prognosis and therapy in HCC. OPEN ACCESS

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Section: Mechanisms Of Mtdh Overexpression In Hccmentioning

confidence: 95%

Section: Role Of Mtdh As An Rna Binding Protein In Drug Resistancementioning

confidence: 99%

Section: Foxm1 Acts As a Therapeutic Target Of Hccmentioning

confidence: 99%

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Role of MTDH, FOXM1 and microRNAs in Drug Resistance in Hepatocellular Carcinoma

et al. 2014

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“…Previous studies have identified that AEG-1 serves a crucial role in tumor progression, including transformation, evasion of apoptosis, invasion, metastasis and chemoresistance (25,26). AEG1 has been reported to be associated with the activation of several signaling pathways including phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor (NF)κB (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Astrocyte elevated gene-1 promotes the proliferation and invasion of breast cancer cells by activating the Wnt/β-catenin signaling pathway

Dai

Wang

et al. 2017

Oncology Letters

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Abstract. Astrocyte elevated gene-1 (AEG1) was identified to be overexpressed in breast cancer, and to be associated with the development of breast cancer. In the present study, AEG1 was identified as highly expressed in the MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines and was detected in the MCF-10A normal breast epithelial cell line. The present study established an AEG1-knockdown MCF-7 cell line to investigate the expression status of certain cancer-associated proteins. Western blotting demonstrated that AEG1 may affect cancer cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway, a hypothesis that has been supported by cell function tests. The results of the present study demonstrated that when AEG1 was significantly overexpressed in breast cancer cells it promoted cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway. Therefore, AEG1 may serve as a novel therapeutic target in breast cancer. IntroductionBreast cancer is a common type of malignancy; the incidence of the disease has increased in recent years worldwide, currently ranking first with respect to cancer-associated morbidity in women (1-3). The traditional methods of treatment include surgery, radiotherapy and chemotherapy for patients with advanced breast cancer exhibit poor efficacy (4). Therefore, the development of gene-targeted therapy for breast cancer requires further attention. Previous studies have revealed that numerous genes are involved in the occurrence and development of breast cancer, including cyclin D1, matrix metalloproteinases (MMPs) and E-cadherin (5-8). Astrocyte elevated gene-1 (AEG1) has also been investigated with respect to poor prognosis in breast cancer (9). AEG1 is a potentially crucial mediator of tumor malignancy and a key converging point of a complex network of oncogenic signaling pathways (10-12). Previous studies revealed that the AEG1 gene was significantly overexpressed in a number of types of malignant cells, and is associated with tumorigenesis, proliferation, invasion and metastasis (13,14). Statistics also demonstrated that AEG1 was upregulated in breast cancer tissue and positively correlated with clinical stage and lymph node metastasis (15).The Wnt signaling pathway is one of the most important intracellular signal transduction pathways, and it affects the activated state of multiple effector molecules downstream (16)(17)(18)(19). It is closely associated with a variety of human tumor developments, and serves an important role in breast cancer cell proliferation and invasion (20,21). However, the mechanisms that underlie the activation of the Wnt signaling pathway in various types of breast cancer have yet to be identified. β-catenin has been revealed as a central regulator in the Wnt signaling pathway, and is associated with disease progression and poor prognosis in breast cancer (22). Typically, during activation of the Wnt signaling pathway, β-catenin accumulates in the cytosol at high levels, binds to T-cell factor/lymphoid enhancer fac...

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“…; also known as AEG-1 and 3D3/LYRIC) has been implicated in many cancer-related processes, including cellular proliferation, survival, invasion, chemoresistance, and metastasis (1)(2)(3). MTDH is located on chromosome 8q22, a region that is frequently amplified in cancers and is correlated with poor survival in patients with breast cancer and hepatocellular carcinoma (4).…”

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confidence: 99%

Genetic Deficiency of Mtdh Gene in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs

Meng

Yang

Zhang

et al. 2015

Journal of Biological Chemistry

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Drug Resistance Mediated by AEG-1/MTDH/LYRIC

Cited by 56 publications

References 81 publications

Role of MTDH, FOXM1 and microRNAs in Drug Resistance in Hepatocellular Carcinoma

Role of MTDH, FOXM1 and microRNAs in Drug Resistance in Hepatocellular Carcinoma

Astrocyte elevated gene-1 promotes the proliferation and invasion of breast cancer cells by activating the Wnt/β-catenin signaling pathway

Genetic Deficiency of Mtdh Gene in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs

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