Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion
Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion
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DOI：
10.1007/s10585-015-9720-7
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发表时间：
2015-06-01
影响因子：
4
通讯作者：
Ruiz, Anna
中科院分区：
文献类型：
--
作者：
Pedrola, Nuria;Devis, Laura;Ruiz, Anna
子宫内膜癌是西方国家女性生殖道最常见的恶性肿瘤。我们的研究小组之前已经确定了子宫内膜癌中转录因子ETV5的上调，在与子宫肌层侵袭相关的肿瘤分期中，转录因子ETV5的上调具有特异性和显着性。我们已经证明，ETV5在Hec1a子宫内膜癌细胞中过表达可以诱导上皮细胞向间充质细胞的转变，从而获得迁移和侵袭能力。在目前的工作中，我们已经确定Nidogen 1(NID1)和核蛋白1(NUPR1)是ETV5在子宫内膜癌细胞中的直接转录靶点。抑制ETV5过表达细胞中的NID1和NUPR1可减少细胞在体外的迁移和侵袭，并减少原位子宫内膜癌模型中肿瘤的生长和扩散。重要的是，我们证实，与其配对的浅表区相比，肿瘤侵袭前沿的NUPR1和NID1蛋白表达显著增加，伴随着ETV5的过度表达。总之，我们得出结论，NID1和NUPR1是ETV5的新靶点，并在肿瘤侵袭前沿积极与ETV5合作，获得侵袭表型，共同推动子宫内膜癌的侵袭。
Endometrial cancer is the most frequent malignancy of the female genital tract in western countries. Our group has previously characterized the upregulation of the transcription factor ETV5 in endometrial cancer with a specific and significant increase in those tumor stages associated with myometrial invasion. We have shown that ETV5 overexpression in Hec1A endometrial cancer cells induces epithelial to mesenchymal transition resulting in the acquisition of migratory and invasive capabilities. In the present work, we have identified Nidogen 1 (NID1) and Nuclear Protein 1 (NUPR1) as direct transcriptional targets of ETV5 in endometrial cancer cells. Inhibition of NID1 and NUPR1 in ETV5 overexpressing cells reduced cell migration and invasion in vitro and reduced tumor growth and dissemination in an orthotopic endometrial cancer model. Importantly, we confirmed a significant increase of NUPR1 and NID1 protein expression in the invasion front of the tumor compared to their paired superficial zone, concomitant to ETV5 overexpression. Altogether, we conclude that NID1 and NUPR1 are novel targets of ETV5 and are actively cooperating with ETV5 at the invasion front of the tumor in the acquisition of an invasive phenotype to jointly drive endometrial cancer invasion.