Cyclin-dependent kinase 5 controls vasculogenic mimicry formation in non-small cell lung cancer via the FAK-AKT signaling pathway

被引:21
作者
Zhou, Xiaoshu [1 ]
Gu, Runxia [1 ,3 ,4 ,5 ]
Han, Xiaoming [2 ]
Wu, Gang [1 ]
Liu, Junli [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Canc Ctr, Wuhan 430022, Hubei, Peoples R China
[2] Jingmen Second People Hosp, Dept Ultrasonog, Jingmen 448000, Peoples R China
[3] Chinese Acad Med Sci, Inst Hematol, Tianjin 300020, Peoples R China
[4] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin 300020, Peoples R China
[5] Peking Union Med Coll, Tianjin 300020, Peoples R China
基金
中国国家自然科学基金;
关键词
Vasculogenic mimicry; Cyclin-dependent kinase 5; Non-small cell lung cancer; Tumor plasticity; FAK; TUMOR ANGIOGENESIS;
D O I
10.1016/j.bbrc.2017.08.076
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vasculogenic mimicry (VM), an endothelial-independent tumor vascularization phenomenon Fepre,senting functional tumor plasticity, might be the culprit behind the poor clinical outcome in classic. antiangiogenesis treatment. However, the mechanism underlying VM needs to be elucidated. Cyclindependent kinase 5 (CDK5) has been recognized as a key factor in regulating migration and neuronal plasticity. Recently, CDK5 was associated with tumor migration and invasion and its expression levels correlated with poor clinical prognosis, indicating its important role in tumor cell plasticity. In this study, we determined the presence of VM network in the lung cancer cell line A549 by tube formation assay. Selective inhibition of CDK5 expression by roscovitine or siRNA significantly decreased VM formation in A549 cells both in vitro and in vivo and retarded tumor growth. To investigate the possible mechanism, we detected the downstream pathway of CDK5 by Western blotting and immunohistochemistry. We found that CDK5 silencing led to significant decrease in FAKSer732 and AnSer472phosphorylation level. Further studies showed that FAK knockdown impaired VM formation and deregulated cytoskeleton transformation of A549 cells. And these effects caused by FAR silence couldn't be reversed by adding CDK5 recombinant protein. This study indicates that CDK5 kinase activates the FAK/AKT signaling pathway to generate VM in a lung cancer cell line, which can help us develop potential therapeutic strategies against vessel-positive tumors. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:447 / 452
页数:6
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