AEG-1 Is a Target of Perifosine and Is Over-Expressed in Gastric Dysplasia and Cancers

Huang, Wenbin; Yang, Li; Song, Lina; Liu, Dongxiao; Chen, Xi; Ma, Zhuo; Zhai, Sulan; Li, Ping; Wang, Xuerong

doi:10.1007/s10620-013-2735-5

Cited by 23 publications

(37 citation statements)

References 24 publications

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“…We have previously reported that AEG‐1 was overexpressed in gastric dysplasia and cancer among 87 cases of gastric adenocarcinoma, 60 cases of dysplasia and 47 cases of normal gastric mucosal tissues; however, we did not analyse its correlation with metastasis 16. In the present study, we re‐read these sections with AEG‐1 immunostaining and performed statistical analyses.…”

Section: Discussionmentioning

confidence: 88%

“…We previously reported that transient knockdown of AEG‐1 expression by siRNA inhibited the growth of gastric cancer cells 16. To further explore the role of AEG‐1 in metastastatic cells, we established two pairs of AEG‐1 stable knockdown cell lines in SGC7901 and MGC803 cells, as they had elevated expression of AEG‐1 and are commonly used for migration and invasion studies 16, 30.…”

Section: Resultsmentioning

confidence: 99%

“…We also found that eIF4E expression was increased in gastric tumour tissue compared with adjacent non‐cancerous tissue, and its overexpression was correlated with distant metastasis 30. Moreover, both of these important molecules are targets of perifosine, a synthetic alkylphosphocholine that inhibits Akt signalling 16, 30. As AEG‐1 is reported to be located downstream of PI3K/Akt and to function as a transcriptional factor, we suspected that eIF4E may be transcriptionally regulated by AEG‐1.…”

Section: Introductionmentioning

confidence: 83%

“…We previously reported that AEG‐1 is up‐regulated in gastric dysplasia and cancer, and its high expression is correlated with the Lauren classification ( P = 0.027), the T classification ( P = 0.001), the N classification ( P = 0.002) and pTNM staging ( P = 0.043) 16. We also found that eIF4E expression was increased in gastric tumour tissue compared with adjacent non‐cancerous tissue, and its overexpression was correlated with distant metastasis 30.…”

Section: Introductionmentioning

confidence: 96%

“…AEG‐1/MTDH was subsequently found to mediate the metastasis of breast cancer 8. In recent years, AEG‐1 expression was found to be elevated and correlated with clinical tumour type, stage, metastasis and prognosis in a variety of cancers, including breast 9, lung 10, colorectal 11, cervical 12, 13, head and neck 14, hepatocellular 15 and gastric cancers 16, 17. AEG‐1 has been shown to be transcriptionally up‐regulated by Ha‐Ras‐activated PI3K and c‐Myc 18.…”

Section: Introductionmentioning

confidence: 99%

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AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression

Yang

et al. 2017

J Cellular Molecular Medi

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Gastric cancer is the third leading cause of cancer‐related deaths worldwide, and patients with lymph node, peritoneal and distant metastasis have a poor prognosis. Overexpression of Astrocyte‐elevated gene‐1 (AEG‐1) has been reported to be correlated with the progression and metastasis of gastric cancer. However, its mechanisms are quite unclear. In this study, we found that elevated expression of AEG‐1 was correlated with metastasis in human gastric cancer tissues. Moreover, gain‐ or loss‐of‐function of AEG‐1, respectively, promoted or suppressed epithelial–mesenchymal transition (EMT), migration and invasion of gastric cancer cells. AEG‐1 positively regulated eIF4E, MMP‐9 and Twist expression. Manipulating eIF4E expression by transfection of overexpression constructs or siRNAs partially eliminated AEG‐1‐regulated EMT, cell migration and invasion. In addition, overexpression or knockdown of eIF4E promoted or suppressed EMT, cell migration and invasion in parallel with upregulation of MMP‐9 and Twist expression, while manipulating eIF4E expression partially abrogated AEG‐1‐induced MMP‐9 and Twist. Finally, silencing of AEG‐1 expression not only inhibited tumour growth in parallel with downregulation of eIF4E, MMP‐9 and Twist expression in a xenograft nude mouse model, but also suppressed lymph node and peritoneal metastasis of gastric cancer in an orthotopic nude mouse model. These findings suggest that AEG‐1 promotes gastric cancer metastasis through upregulation of eIF4E‐mediated MMP‐9 and Twist, which provides new diagnostic markers and therapeutic targets for cancer metastasis.

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Section: Discussionmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression

Yang

et al. 2017

J Cellular Molecular Medi

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Targeted therapies in pancreatic cancer: Promises and failures

Bagherabad

Afzaljavan

Shahidsales

et al. 2018

J of Cellular Biochemistry

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Pancreatic ductal adenocarcinoma (PDAC) is an incidence rate nearly equal to its mortality rate. The poor prognosis of the disease can be explained by the absence of effective biomarkers for screening and early detection, together with the aggressive behavior and resistance to the currently available chemotherapy. The therapeutic failure can also be attributed to the inter-/intra- tumor genetic heterogeneity and the abundance of tumor stroma that occupies the majority of the tumor mass. Gemcitabine is used in the treatment of PDAC, however, the response rate is less than 12%. A recent phase III trial revealed that the combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin could be an option for the treatment of metastatic PDAC patients with good performance status, although these approaches can be resulted high toxicity level. Further investigations are required to develop innovative anticancer agents that either improve gemcitabine activity, within novel combinatorial approaches, or acts with a better efficacy than gemcitabine. The aim of the current review is to give an overview about preclinical andclinical studies targeting key dysregulated signaling pathways in PDAC. This article is protected by copyright. All rights reserved.

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Lobetyolin inhibits cell proliferation and induces cell apoptosis by downregulating ASCT2 in gastric cancer

Cheng,

Zhai,

et al. 2023

Cytotechnology

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AEG-1 Is a Target of Perifosine and Is Over-Expressed in Gastric Dysplasia and Cancers

Cited by 23 publications

References 24 publications

AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression

AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression

Targeted therapies in pancreatic cancer: Promises and failures

Lobetyolin inhibits cell proliferation and induces cell apoptosis by downregulating ASCT2 in gastric cancer

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