Dysregulated ENPP1 increases the malignancy of human lung cancer by inducing epithelial-mesenchymal transition phenotypes and stem cell features

American Journal of Cancer Research

Dongliang Xu¹  Yueling Liao²  Tong Wang³  Hongyong Song⁴  Min Hu⁵  Wenzheng Guo⁶  Beibei Sun⁷ 

[1] Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China;Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China;Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Translational Medical Research Center, Shanghai Jiao Tong University, Shanghai, China

关键词: ENPP1;    lung cancer;    EMT;    stemness;    migration;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

CC BY-NC