Overexpression of astrocyte-elevated gene-1 is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through up-regulation of matrix metalloproteinase-9 expression.
Expression of astrocyte-elevated gene-1, a novel oncoprotein, is elevated in multiple cancers and plays a vital role in tumor cell growth, invasion, angiogenesis, and progression to metastasis. However, the functional significance of astrocyte-elevated gene-1 in non-small cell lung cancer still remains unclear. Our present study showed that the markedly up-regulated expression of astrocyte-elevated gene-1 was observed in non-small cell lung cancer cell lines and tissues at the level of both transcription and translation. Simultaneously, ectopic expression or small interfering RNA silencing of astrocyte-elevated gene-1 markedly enhanced or inhibited the invasive ability of non-small cell lung cancer cells, respectively. At the molecular level, we also revealed that the function of astrocyte-elevated gene-1 in promoting metastasis was associated with the activation of matrix metalloproteinase-9 expression. Consistent with these observations, immunostaining analysis revealed a significant positive correlation between astrocyte-elevated gene-1 and matrix metalloproteinase-9. Moreover, subcutaneous xenografts of non-small cell lung cancer cells engineered to express astrocyte-elevated gene-1 were highly invasive compared with the parental cells and expressed a high level of matrix metalloproteinase-9. In archival non-small cell lung cancer specimens, high astrocyte-elevated gene-1 expression correlated significantly with clinical staging (P = .048), differentiation (P = .023), and lymph node metastasis (P = .032). The overall survival time in patients with high astrocyte-elevated gene-1 expression was notably shorter than that in patients with low astrocyte-elevated gene-1 expression (P < .001). Taken together, our results indicate that astrocyte-elevated gene-1 plays a crucial role in the carcinogenesis and aggressiveness of non-small cell lung cancer, promoting its metastasis by modulating matrix metalloproteinase-9 expression and leading to a poor clinical prognosis.
Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong 510080, People's Republic of China.
Shijun
S
Sun
Zunfu
Z
Ke
Fen
F
Wang
Shuhua
S
Li
Wenfang
W
Chen
Anjia
A
Han
Zuo
Z
Wang
Huijuan
H
Shi
Lian-Tang
LT
Wang
Xiaodong
X
Chen
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D016601:RNA-Binding Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9