MilliporeSigma
  • Home
  • Search Results
  • Cyclin-dependent kinase 5 controls vasculogenic mimicry formation in non-small cell lung cancer via the FAK-AKT signaling pathway.

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

Biochemical and biophysical research communications (2017-08-27)
Xiaoshu Zhou, Runxia Gu, Xiaoming Han, Gang Wu, Junli Liu
ABSTRACT

Vasculogenic mimicry (VM), an endothelial-independent tumor vascularization phenomenon representing 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. Cyclin-dependent 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 FAKSer732and AKTSer472phosphorylation level. Further studies showed that FAK knockdown impaired VM formation and deregulated cytoskeleton transformation of A549 cells. And these effects caused by FAK 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
ECM Gel from Engelbreth-Holm-Swarm murine sarcoma, liquid, BioReagent, suitable for cell culture
Sigma-Aldrich
Monoclonal Anti-CDK5 antibody produced in mouse, clone 1A2, ascites fluid