Repression of metadherin inhibits biological behavior of prostate cancer cells and enhances their sensitivity to cisplatin

Wei, Yongbao; Guo, Qian; Gao, Yunliang; Yan, Bin; Zhao, Wang; Yang, Jin; Liu, Wei

doi:10.3892/mmr.2015.3357

Cited by 8 publications

(5 citation statements)

References 29 publications

(47 reference statements)

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“…This approach induced a CD8+ T cell-mediated immune response inhibiting tumor growth and metastasis and increased the chemosensitivity to paclitaxel with a prolongation of the survival time [ 237 ]. The inhibition of AEG-1 in prostate cancer cells increased the sensitivity to cisplatin through modulating the PI3K/AKT pathway [ 238 ].…”

Section: Role Of Aeg-1 In Cancer Drug Resistancementioning

confidence: 99%

Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Manna

Sarkar

2021

Cancers

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Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.

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Section: Role Of Aeg-1 In Cancer Drug Resistancementioning

confidence: 99%

Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Manna

Sarkar

2021

Cancers

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“…Growing evidence reveals that AEG-1 is significantly related to the invasion, migration, apoptosis and prognosis of different cancers, such as hepatocellular carcinoma [9], bladder cancer [10], prostate cancer [11], gastric cancer [12] and so on. Zhou et al [9] found that AEG-1 was highly expressed in high metastatic potential cancer cell lines and the AEG-1 expression was positively correlated with orientation chemotaxis and adhesion of human hepatocellular carcinoma cell lines.…”

Section: Introductionmentioning

confidence: 99%

“…Zhou et al [9] found that AEG-1 was highly expressed in high metastatic potential cancer cell lines and the AEG-1 expression was positively correlated with orientation chemotaxis and adhesion of human hepatocellular carcinoma cell lines. Wei et al [11] found that AEG-1 could act as an oncogene and the inhibition of AEG-1 expression could promote cell apoptosis, reduce cell viability and weaken the invasive ability of prostate cancer cells. In addition, the suppression of AEG-1 expression could improve the cell sensitivity to cisplatin.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance and effect of AEG-1 on the proliferation, invasion, and migration of NSCLC: a study based on immunohistochemistry, TCGA, bioinformatics, in vitro and in vivo verification

Zhang

Hou

et al. 2017

Oncotarget

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BackgroundAstrocyte elevated gene-1 (AEG-1) is related to the tumorigenesis and deterioration of different cancers, including non-small cell lung cancer (NSCLC). However, the effect of AEG-1 in NSCLC remains unclear. In this study, we aimed to investigate the clinical significance and effect of AEG-1 on biological function of NSCLC.ResultsAEG-1 was significantly overexpressed in NSCLC tissues and closely correlated to the deterioration of NSCLC based on tissue microarray, TCGA database and meta-analysis. After knock-down of AEG-1, the proliferation, migration and invasion of NSCLC cells were all inhibited, and the tumorigenic and angiogenic ability of NSCLC cells were weakened. Furthermore, the AEG-1 co-expressed genes were significantly related to AMPK signaling pathway based on bioinformatics approaches.Materials and MethodsA tissue microarray, the Cancer Genome Atlas (TCGA) database, as well as a meta-analysis were performed to analyze the relationship between AEG-1 and the clinicopathological parameters of NSCLC. Furthermore, immunocytochemistry, Western blot analysis, scratch assay, colony formation assay, Transwell migration and invasion assay and the chick embryo chorioallantoic membrane (CAM) model were conducted to explore the effect of AEG-1 on NSCLC in vitro and in vivo. Additionally, bioinformatics analyses were carried out to assess the potential pathways and networks of the co-expressed genes of AEG-1.ConclusionsAEG-1 is positively activated in the tumorigenesis and deterioration of NSCLC. We hypothesize that AEG-1 could play an important role in NSCLC via AMPK signaling pathway. Inhibiting the expression of AEG-1 is expected to become a novel method in the therapeutic strategies of NSCLC.

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“…Secondly, MTDH may inhibit the expression of cell cycle protein inhibitors, including p53, p21 and p27 and induce the expression of cell cycle promoting proteins, including cyclin D1 and cyclin E (37). In prostate cancer, the inhibition of MTDH promoted apoptosis, reduced cell viability and increased cell sensitivity to cisplatin (38). MTDH may also promote human cancer growth by regulating the expression of specific miRNAs (39).…”

Section: Discussionmentioning

confidence: 99%

Metadherin overexpression in perihilar cholangiocarcinoma is associated with lymph node metastasis and poor prognosis

et al. 2019

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Metadherin (MTDH) is a protein that is also named astrocyte elevated gene-1, and is highly expressed in a number of different tumor tissues. Although the expression of MTDH is associated with tumor invasion and recurrence, the expression of this protein in perihilar cholangiocarcinoma (PCCA) and its clinical use have not yet been investigated. In the present study, the expression of MTDH in patients with PCCA was investigated in order to determine its clinicopathological use. An immunohistochemical method was used to detect MTDH expression and the epithelial-mesenchymal transition markers E-cadherin and vimentin in 66 cases of PCCA. In addition to the expression of MTDH, the clinical and pathological data and the postoperative outcomes were analyzed. The MTDH positive expression rate was 48.5% (32/66) in PCCA. A significantly higher MTDH expression level was identified in the poor tumor differentiation group compared with the well differentiation group (P=0.007). In the positive lymph node metastasis group, a significantly higher MTDH expression level was revealed compared with the negative lymph node metastasis group (P=0.023). No association was noted with regard to the expression of MTDH and the variables age, sex, tumor diameter, tumor grade and tumor classification stage. Positive MTDH expression was significantly associated with high vimentin expression (P=0.037) compared with negative vimentin expression and inversely associated with positive E-cadherin expression compared with negative E-cadherin expression (P=0.030). Survival analysis suggested that the high MTDH expression group was associated with a worse overall survival (OS) rate and recurrence free survival (RFS) rate compared with the low MTDH expression group (P<0.001 and P=0.01, respectively). Cox regression analysis indicated that the Tumor-Node-Metastasis, surgery margin and high MTDH expression were independent OS and RFS factors for PCCA. MTDH expression may serve an important function in PCCA tumor growth and metastasis. Targeting MTDH may have important therapeutic applications for patients with PCCA.

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Repression of metadherin inhibits biological behavior of prostate cancer cells and enhances their sensitivity to cisplatin

Cited by 8 publications

References 29 publications

Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Clinical significance and effect of AEG-1 on the proliferation, invasion, and migration of NSCLC: a study based on immunohistochemistry, TCGA, bioinformatics, in vitro and in vivo verification

Metadherin overexpression in perihilar cholangiocarcinoma is associated with lymph node metastasis and poor prognosis

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