Over‐expression of AEG‐1 significantly associates with tumour aggressiveness and poor prognosis in human non‐small cell lung cancer

Abstract

Astrocyte elevated gene 1 (AEG-1), a novel oncoprotein, has been implicated in oncogenesis and cancer progression in various types of human cancers. The clinical significance and biological role of AEG-1 in non-small cell lung cancer (NSCLC), however, remain unclear. In the present study, we found that the expression of AEG-1 was markedly up-regulated in NSCLC cell lines and NSCLC tissues at the level of both transcription and translation. Ectopically expressed AEG-1 enhanced the migratory and invasive abilities of NSCLC cells, whereas knockdown of endogenous AEG-1 by specific shRNAs significantly inhibited these abilities. The function of AEG-1 on metastasis modulation was associated with the activation of the PI3K-Akt and NF-kappaB signalling pathways. Furthermore, we showed high expression of AEG-1 in 99/200 (49.5%) paraffin-embedded archival NSCLC specimens. Moreover, statistical analysis displayed a significant correlation in AEG-1 expression with the clinical stage (p < 0.001), T classification (p = 0.001), N classification (p = 0.015), distant metastasis (p = 0.004) and differentiation (p = 0.027). Patients with higher AEG-1 expression had an overall shorter survival time, whereas patients with lower expression of AEG-1 had a better survival time. Multivariate analysis suggested that AEG-1 expression might be an independent prognostic indicator for the survival of NSCLC patients. Taken together, our results suggest that elevated expression of AEG-1 plays an important role in the aggressiveness of NSCLC, leading to a poor clinical outcome.

Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression

“…Recently, numerous studies have demonstrated that AEG-1 is upregulated and correlated with the progression and prognosis of the patients [6][7][8]. In order to investigate whether AEG-1 also plays a role in RCC, we performed the current study.…”

“…It is very clear now that AEG-1 is far more than just a gene regulated in astrocytes which contributes centrally to human gliomas. Numerous studies confirmed that it is also over-expressed in various human cancers including breast, lung, prostate, glioblastoma multiform and esophageal cancer [6][7][8][9][10]. AEG-1 plays an important role in PI3K/Akt signaling pathway and nuclear factor κ-B signaling pathway which regulate fundamental cellular functions, including proliferation, growth and survival, thus have critical function in cancer cell migration and invasion [11,12].…”

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

“…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.…”

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

“…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.…”