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Endothelial progenitor cells contribute to neovascularization of non‐small cell lung cancer via histone deacetylase 7‐mediated cytoskeleton regulation and angiogenic genes transcription
Author(s) -
Wei Ye,
Zhou Fangzheng,
Zhou Haibo,
Huang Jing,
Yu Dandan,
Wu Gang
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31349
Subject(s) - cancer research , histone deacetylase , progenitor cell , microbiology and biotechnology , biology , neovascularization , angiogenesis , endothelial stem cell , histone , gene , stem cell , genetics , in vitro
To supply tumor tissues with nutrients and oxygen, endothelial progenitor cells (EPCs) home to tumor sites and contribute to neovascularization. Although the precise mechanism of EPCs‐induced neovascularization remains poorly understood in non‐small cell lung cancer (NSCLC), histone deacetylase 7 (HDAC7) is considered as a critical regulator. To explore the function of HDAC7 in neovascularization induced by EPCs, tube formation assay, immunofluorescence, microarray, Western blot analysis and animal models were performed. In vitro , HDAC7 abrogation led to the activation of Rho‐associated coiled‐coil containing protein kinase/myosin light chain 2 pathway concomitant with ERK dephosphorylation, causing the instability of cytoskeleton and collapse of tube formation. In vivo , absence of HDAC7 impaired the vascular lumen integrity and decreased the functional blood perfusion, inhibiting the growth of tumor. At the level of transcription, HDAC7 silencing upregulated antiangiogenic genes and suppressed proangiogenic genes collectively, turning off the angiogenic switch during vessel formation. Taken together, HDAC7 plays a dual role in maintaining the structural and nonstructural functions of EPCs. Our work demonstrates the molecular mechanism by which HDAC7 contributes to the angiogenic property of EPCs and provides a rational basis for specific targeting of antiangiogenic strategies in lung cancer.