Open AccessHistone deacetylase 3 expression correlates with vasculogenic mimicry through the phosphoinositide3‐kinase / ERK– MMP –laminin5γ2 signaling pathway
Author(s) -
Liu Xiao,
Wang JiHui,
Li Shun,
Li LinLin,
Huang Min,
Zhang YongHong,
Liu Yang,
Yang YuanTao,
Ding Rui,
Ke YiQuan
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12684
Subject(s) - vasculogenic mimicry , mapk/erk pathway , glioma , histone deacetylase , cancer research , signal transduction , hdac1 , microbiology and biotechnology , biology , kinase , mek inhibitor , chemistry , histone , cancer , biochemistry , metastasis , genetics , gene
Vasculogenic mimicry ( VM ) refers to the process by which highly aggressive tumor cells mimic endothelial cells to form vessel‐like structures that aid in supplying enough nutrients to rapidly growing tumors. Histone deacetylases ( HDAC s) regulate the expression and activity of numerous molecules involved in cancer initiation and progression. Notably, HDAC 3 is overexpressed in the majority of carcinomas. However, thus far, no data are available to support the role of HDAC 3 in VM . In this study, we subjected glioma specimens to immunohistochemical and histochemical double‐staining methods and found that VM and HDAC 3 expression were related to the pathological grade of gliomas. The presence of VM correlated with HDAC 3 expression in glioma tissues. The formation of tubular structures, as determined by the tube formation assay to evaluate VM , was impaired in U87 MG cells when transfected by si RNA or treated with an HDAC 3 inhibitor. Importantly, the expression of VM ‐related molecules such as MMP ‐2/14 and laminin5γ2 was also affected when HDAC 3 expression was altered. Furthermore, U87 MG cells were treated with a phosphoinositide 3‐kinase ( PI 3K) inhibitor or/and ERK inhibitor and found that the PI 3K and ERK signaling pathways play key roles in VM ; whereas, in VM , the two signaling pathways did not act upstream or downstream from each other. Taken together, our findings showed that HDAC 3 contributed to VM in gliomas, possibly through the PI 3K/ ERK – MMP s–laminin5γ2 signaling pathway, which could potentially be a novel therapeutic target for gliomas.