EFEMP1 promotes ovarian cancer cell growth, invasion and metastasis via activated the AKT pathway.
EFEMP1 promotes ovarian cancer cell growth, invasion and metastasis via activated the AKT pathway.
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DOI：
10.18632/oncotarget.10296
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
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作者：
Yin X;Fang S;Wang M;Wang Q;Fang R;Chen J
EFEMP 1是一种细胞外基质蛋白，与多种肿瘤的发生发展密切相关。然而，其在卵巢癌中的功能仍不清楚。在我们的研究中，我们进行了cDNA微阵列分析，并确定EFEMP 1显着升高，在高侵袭性亚克隆，与低侵袭性亚克隆。随后构建慢病毒转染实验。结果表明，敲低EFEMP 1显著抑制卵巢癌细胞增殖，并诱导细胞周期停滞在G1/G 0期。我们还发现，降低磷酸化AKT的活性可以抑制细胞的侵袭和转移。同时，EFEMP 1过表达诱导的磷酸化AKT活性的增加显著增强了卵巢癌细胞的侵袭和迁移能力。此外，裸鼠体内模型证实EFEMP 1与肿瘤的发生密切相关。RT 2 Profiler EMT PCR阵列结果进一步表明，EFEMP 1的减少抑制了上皮向间质转化（EMT）。总之，EFEMP 1通过激活AKT信号通路，作为一种正性调节因子参与卵巢癌的侵袭和转移。总体而言，EFEMP 1在卵巢癌新的治疗策略的开发中显示出潜在的用途。
EFEMP1, a kind of extracellular matrix (ECM) protein, has been suggested to correlate with the development of different types of carcinoma. However, its functions in ovarian cancer remain unclear. In our study, we performed cDNA microarray analysis and identified EFEMP1 dramatically elevated in the highly invasive subclone, compared with the low invasive subclone. Lentivirus transfection experiments were constructed afterwards. The results demonstrated that knockdown of EFEMP1 significantly inhibited ovarian cancer cell proliferation and induced cell cycle arrest at the G1/G0 phase. We also found that decreased the activity of phospho-AKT could suppress cell invasion and metastasis. Meanwhile, the increased phospho-AKT activity induced by the overexpression of EFEMP1 had significantly enhanced the abilities of ovarian cancer cells to invade and migrate. In addition, the vivo nude mice model confirmed that EFEMP1 was tightly correlated with the development of tumor. The results of RT2 Profiler EMT PCR array further indicated that decreased EFEMP1 suppressed epithelial-to-mesenchymal transition (EMT). Collectively, by activating AKT signaling pathway, EFEMP1 contributed to ovarian cancer invasion and metastasis as a positive regulator. Overall, EFEMP1 had showed the potential use in the development of new therapeutic strategies for ovarian cancer.