Ursolic acid inhibits epithelial–mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells

Liu, Kunmei; Guo, Le; Ma, Lin; Bao, Weiwei; Yang, Jue; Li, Xiaokang; Xi, Tao; Zhao, Wei

doi:10.1097/cad.0b013e328360093b

Cited by 35 publications

(29 citation statements)

References 32 publications

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“…the involvement of AEG-1 in EMT of hepatocellular carcinoma and nonYsmall cell lung cancer. 15,16 Intriguingly, the signal mechanisms related to the association of AEG-1 with EMT in cervical cancer has never been explored.…”

Section: Discussionmentioning

confidence: 99%

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Astrocyte Elevated Gene-1 Promotes Progression of Cervical Squamous Cell Carcinoma by Inducing Epithelial-Mesenchymal Transition via Wnt Signaling

Song

Xiong

et al. 2015

International Journal of Gynecological Cancer

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ObjectiveThe aim of this study was to investigate the association of astrocyte elevated gene-1 (AEG-1) with epithelial-mesenchymal transition of cervical squamous cell carcinoma (CSCC) and the underlying mechanisms.MethodsThe expression of proteins was determined by immunohistochemistry in tissues. Overexpression and knockdown of AEG-1 in SiHa cells were achieved by stable AEG-1 gene transfection (SiHa-AEG-1+) and AEG-1-siRNA (SiHa-AEG-1−), respectively. The cellular levels of messenger RNA and proteins were assessed with reverse transcription polymerase chain reaction and Western blotting, respectively. The cell invasion capacity was assessed by the chamber invasion assay.ResultsAEG-1 was overexpressed in clinical CSCC and associated with lymph node metastasis, parametrial involvement, stromal invasion, and vascular invasion. A high level of vimentin and a low level of E-cadherin were also detected in the cancer tissues. AEG-1 expression was positively correlated with vimentin expression and negatively with E-cadherin expression in CSCC tissues. In addition, high level of AEG-1 was related to unfavorable prognosis of CSCC. On a cellular level, overexpression of AEG-1 was found to lead to an up-regulation of vimentin and a down-regulation of E-cadherin on messenger RNA and protein level in SiHa cells, whereas AEG-1 knockdown led to a contrary result. Meanwhile, the nuclear levels of NF-κB p65 and β-catenin were also increased in SiHa-AEG-1+, whereas their nuclear levels were decreased in SiHa-AEG-1−. Inhibition of Wnt signaling significantly reduced vimentin level and enhanced E-cadherin level in SiHa-AEG+, but inhibition of NF-κB signaling did not. SiHa-AEG-1+ and SiHa-AEG− showed an enhanced and a decreased invasive capacity, respectively. The enhanced invasiveness of SiHa-AEG-1+ was weakened by inhibition of Wnt signaling.ConclusionsAEG-1 was associated with the progression of CSCC by promoting epithelial-mesenchymal transition via Wnt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

“…15,16 However, the implications of AEG-1 for EMT of cervical carcinoma remain unclear. The aim of this study was to investigate the association of AEG-1 with EMT of CSCC and elucidate the related signal mechanisms.…”

mentioning

confidence: 99%

Astrocyte Elevated Gene-1 Promotes Progression of Cervical Squamous Cell Carcinoma by Inducing Epithelial-Mesenchymal Transition via Wnt Signaling

Song

Xiong

et al. 2015

International Journal of Gynecological Cancer

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“…Current and future studies must focus on the translational aspects of AEG-1/MTDH, and on the understanding of AEG-1/MTDH function in physiological and pathological processes using transgenic and knockout mouse models in cancer. The knockdown of AEG-1/MTDH (32,33,41,45,51,93,94) or AEG-1/MTDH inhibition (92,95,96) can inhibit transformation, proliferation, the evasion of apoptosis, migration and invasion, metastasis, angiogenesis and chemoresistance. In summary, the functional characterization of AEG-1/MTDH as a novel protein with poorly-characterized functions is urgently required to realize its full therapeutic potential.…”

Section: Clinical Translation and Therapeutic Targeting Strategymentioning

confidence: 99%

Progress of cancer research on astrocyte elevated gene-1/Metadherin (Review)

Huang

2014

Oncology Letters

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Tumor development is initiated by an accumulation of numerous genetic and epigenetic alterations that promote tumor initiation, invasion and metastasis. Astrocyte elevated gene-1 [AEG-1; also known as Metadherin (MTDH) and Lysine-rich CEACAM1 co-isolated (LYRIC)] has emerged in recent years as a potentially crucial mediator of tumor malignancy, and a key converging point of a complex network of oncogenic signaling pathways. AEG-1/MTDH has a multifunctional role in tumor development that has been found to be involved in the following signaling cascades: i) The Ha-Ras and PI3K/Akt pathways; ii) the nuclear factor-κB signaling pathway; iii) the ERK/mitogen-activated protein kinase and Wnt/β-catenin pathways; and iv) the Aurora-A kinase signaling pathway. Studies have established that AEG-1/MTDH is crucial in tumor progression, including transformation, the evasion of apoptosis, invasion, angiogenesis and metastasis. In addition, recent clinical studies have convincingly associated AEG-1/MTDH with tumor progression and poor prognosis in a number of cancer types, including hepatocellular, esophageal squamous cell, gallbladder and renal cell carcinomas, breast, non-small cell lung, prostate, gastric and colorectal cancers, and glioma, melanoma, neuroblastoma and osteosarcoma. AEG-1/MTDH may be used as a biomarker to identify subgroups of patients who require more intensive treatments and who are likely to benefit from AEG-1/MTDH-targeted therapies. The therapeutic targeting of AEG-1/MTDH may simultaneously block metastasis, suppress tumor growth and enhance the efficacy of chemotherapeutic treatments.

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“…They found increased expression in E-cadherin as well as decreased expression in N-cadherin and vimentin, which are responsible for the epithelial-mesenchymal transition (EMT). Additionally, UA inhibits metastasis by decreasing the expression of astrocyte elevated gene-1 (AEG-1) and inhibiting NF-κB [40]. In another study, Prasad et al revealed that UA considerably decreases tumor volume in vivo and downregulates metastatic protein expression (e.g., MMP-9, VEGF, and ICAM-1) in vitro [41].…”

Section: Anti-metastasismentioning

confidence: 99%