ING5 inhibits cancer aggressiveness via preventing EMT and is a potential prognostic biomarker for lung cancer.
ING5 inhibits cancer aggressiveness via preventing EMT and is a potential prognostic biomarker for lung cancer.
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ING5 通过阻止 EMT 来抑制癌症侵袭性，是肺癌的潜在预后生物标志物。
DOI：
10.18632/oncotarget.3842
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发表时间：
2015-06-30
期刊：
影响因子：
--
通讯作者：
Zhang T
中科院分区：
文献类型：
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作者：
Zhang F;Zhang X;Meng J;Zhao Y;Liu X;Liu Y;Wang Y;Li Y;Sun Y;Wang Z;Mei Q;Zhang T
生长抑制剂 (ING) 候选肿瘤抑制家族的蛋白质参与多种细胞功能，例如细胞周期调节、细胞凋亡和染色质重塑。 ING5是该家族的新成员，其在肿瘤抑制中的实际作用尚不清楚。在这里，我们发现肺癌 A549 细胞中 ING5 的过表达抑制了细胞增殖和侵袭性，而肺癌 H1299 细胞中 ING5 的敲低则促进了细胞的侵袭性。 ING5 过度表达还消除了小鼠异种移植模型中肺癌细胞的肿瘤生长和侵袭能力。进一步研究表明，ING5过表达抑制EMT，表现为mRNA和蛋白水平上E-cadherin增加，N-cadherin、Snail和slug减少，并伴有形态学变化。 cDNA 微阵列和随后的 qRT-PCR 验证表明，ING5 显着下调 EMT（上皮间质转化）诱导基因的表达，包括 CEACAM6、BMP2 和 CDH11。组织芯片临床研究表明，核ING5与肺癌临床分期、淋巴结转移呈负相关。此外，高水平的核 ING5 与更好的预后相关。总而言之，这些发现揭示了 ING5 作为有效的肿瘤抑制因子在肺癌生长和转移中的重要作用。
The proteins of the Inhibitor of Growth (ING) candidate tumor suppressor family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is the new member of the family whose actual role in tumor suppression is not known. Here we show that ING5 overexpression in lung cancer A549 cells inhibited cell proliferation and invasiveness, while ING5 knockdown in lung cancer H1299 cells promoted cell aggressiveness. ING5 overexpression also abrogated tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. Further study showed that ING5 overexpression inhibited EMT indicated by increase of E-cadherin and decrease of N-cadherin, Snail and slug at mRNA and protein levels, which was accompanied with morphological changes. cDNA microarray and subsequent qRT-PCR validation revealed that ING5 significantly downregulated expression of EMT (epithelial to mesenchymal transition)-inducing genes including CEACAM6, BMP2 and CDH11. Clinical study by tissue microarray showed that nuclear ING5 negatively correlated with clinical stages and lymph node metastasis of lung cancer. Furthermore, high level of nuclear ING5 was associated with a better prognosis. Taken together, these findings uncover an important role for ING5 as a potent tumor suppressor in lung cancer growth and metastasis.