Dysregulated ENPP1 increases the malignancy of human lung cancer by inducing epithelial-mesenchymal transition phenotypes and stem cell features
Dysregulated ENPP1 increases the malignancy of human lung cancer by inducing epithelial-mesenchymal transition phenotypes and stem cell features
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ENPP1失调通过诱导上皮-间质转化表型和干细胞特征增加人类肺癌的恶性程度
DOI：
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发表时间：
2019
影响因子：
5.3
通讯作者：
Jiong Deng
中科院分区：
文献类型：
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作者：
Min Hu;Wenzheng Guo;Yueling Liao;Dongliang Xu;Beibei Sun;Hongyong Song;Tong Wang;Yanbin Kuang;Bo Jing;Kaimi Li;Jing Ling;Feng Yao;Jiong Deng
肿瘤干细胞（CSC）特征和上皮间质转化（EMT）特征的诱导在肿瘤的发生、发展和转移中至关重要。然而，基本机制仍然不完全清楚。在这里，我们发现ENPP 1在诱导和维持肺癌EMT表型和CSC特征中起重要作用。ENPP 1在肺癌细胞中上调。在肺癌HCC 827细胞和A549细胞中ENPP 1的敲低导致抑制的集落形成、体外非锚定依赖性生长和体内致瘤性。ENPP 1敲除还降低了CSC标记物的表达，包括ABCG 2、SOX 2、NANOG和CD 44。此外，ENPP 1敲低逆转了TGFβ诱导的EMT表型，包括细胞迁移、E-钙粘蛋白抑制和波形蛋白诱导。最后，与邻近的正常肺组织相比，在大多数人肺肿瘤组织中鉴定出上调的ENPP 1。综上所述，我们的研究表明，ENPP 1的失调通过诱导CSC特征和EMT样表型而导致人类肺癌恶性程度的增加。
Induction of cancer stem cell (CSC) characters and epithelial mesenchymal transition (EMT) features are crucial in tumor initiation, progression and metastasis. However, underlying mechanisms remain incompletely understood. Here, we showed that ENPP1 plays an important role in inducing and maintaining EMT phenotypes and CSC features in lung cancer. ENPP1 is upregulated in lung cancer cells. ENPP1-knockdown in lung cancer HCC827 cells and A549 cells resulted in suppressed colonogenic formation, anchorage-independent growth in vitro, and tumorigenicity in vivo. ENPP1-knockdown also reduced expression of CSC makers, including ABCG2, SOX2, NANOG, and CD44. Moreover, ENPP1-knockdown reversed TGFβ-induced EMT phenotypes, including cell migration, E-cadherin repression and vimentin induction. Finally, upregulated ENPP1 was identified in majority of human lung tumor tissues compared to adjacent normal lung tissues. Taken together, our study demonstrates that dysregulated ENPP1 contributes to increased malignancy of human lung cancer by inducing CSC-features, and EMT-like phenotypes.