L1CAM promotes vasculogenic mimicry formation by miR-143-3p-induced expression of hexokinase 2 in glioma.
L1CAM promotes vasculogenic mimicry formation by miR-143-3p-induced expression of hexokinase 2 in glioma.
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L1CAM 通过 miR –143 –3p – 诱导神经胶质瘤中己糖激酶 2 的表达促进血管生成拟态形成
DOI：
10.1002/1878-0261.13384
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发表时间：
2023-04
影响因子：
6.6
通讯作者：
Yang, Xiaojun
中科院分区：
文献类型：
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作者：
Huang, Yishan;Zhu, Chenchen;Liu, Pei;Ouyang, Fan;Luo, Juanjuan;Lu, Chunjiao;Tang, Bo;Yang, Xiaojun
In recent decades, antiangiogenic therapy, which blocks the supply of oxygen and nutrition to tumor cells, has become a promising clinical strategy for the treatment of patients with tumors. However, recent studies revealed that vasculogenic mimicry (VM), which is the process by which vascular morphological structures are formed by highly invasive tumor cells, has been considered a potential factor for the failure of antiangiogenic therapy in patients with tumors. Thus, inhibition of VM formation might be a potential target for improving the outcome of antiangiogenic strategies. However, the mechanism underlying VM formation is still incompletely elucidated. Herein, we report that L1CAM might be a critical regulator of VM formation in glioma, and might be associated with the resistance of glioma to antiangiogenic therapy. We found that the tumor‐invasion and tube‐formation capabilities of L1CAM‐overexpressing cells were significantly enhanced in vitro and in vivo. In addition, the results indicated that miR‐143‐3p, which might directly target the 3'UTR of the hexokinase 2 (HK2) gene to regulate its protein expression, was subsequently involved in L1CAM‐mediated VM formation by glioma cells. Further study revealed that the regulation of MMP2, MMP9, and VEGFA expression was involved in this process. Moreover, we identified that activation of the downstream PI3K/AKT signaling pathway of the L1CAM/HK2 cascade is critical for VM formation by glioma cells. Furthermore, we found that the combined treatment of anti‐L1CAM neutralizing monoclonal antibody and bevacizumab increases efficacy beyond that of bevacizumab alone, and suppresses glioma growth in vivo, indicating that the inhibition of L1CAM‐mediated VM formation might efficiently improve the effect of antiangiogenic treatment for glioma patients. Together, our findings demonstrated a critical role of L1CAM in regulating VM formation in glioma, and that L1CAM might be a potential target for ameliorating tumor resistance to antiangiogenic therapy in glioma patients. The authors identified L1CAM as a crucial regulatory factor for modulating vasculogenic mimicry formation in glioma, which might be a potential target for ameliorating tumor resistance to antiangiogenic therapy in glioma patients.
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影响因子：
37.3
作者：
Li Y;Wang H;Sun T;Chen J;Guo L;Shen H;Du Z;Zhou Y
通讯作者：
Zhou Y
乙酰肝素酶通过增强 CD24 表达促进神经胶质瘤进展
影响因子：
6.4
作者：
Barash, Uri;Spyrou, Argyris;Yang, Xiaojun
通讯作者：
Yang, Xiaojun
影响因子：
8
作者：
Bai, Jian;Yeh, Shuyuan;Chang, Chawnshang
通讯作者：
Chang, Chawnshang
影响因子：
4.6
作者：
Garcia, Jesus R.;Gombos, Dan S.;Chevez-Barrios, Patricia
通讯作者：
Chevez-Barrios, Patricia
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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