Int J Biol Sci 2022; 18(3):942-955. doi:10.7150/ijbs.65653 This issue Cite

Research Paper

RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways

Mei Wang1,2,3,6*, Chengfei Zhang2*, Qian Zheng2, Zhijie Ma2, Min Qi1, Guangfu Di1, Shizhang Ling1, Haojun Xu2, Bin Qi4, Chengyun Yao5✉, Hongping Xia2,6✉, Xiaochun Jiang1✉

1. The Translational Research Institute for Neurological Disorders & Interdisciplinary Research Center of Neuromedicine and Chemical Biology of Wannan Medical College and Anhui Normal University, Department of Neurosurgery, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241001, PR China.
2. School of Basic Medical Sciences & State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission & Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical University, Nanjing 211166, PR China.
3. Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, PR China.
4. Department of Neurosurgery, The First Hospital of Jilin University, Changchun130021, PR China.
5. Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing 2100092, PR China.
6. Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing 210009, PR China.
* These authors contributed equally to this work.

Citation:
Wang M, Zhang C, Zheng Q, Ma Z, Qi M, Di G, Ling S, Xu H, Qi B, Yao C, Xia H, Jiang X. RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways. Int J Biol Sci 2022; 18(3):942-955. doi:10.7150/ijbs.65653. https://www.ijbs.com/v18p0942.htm
Other styles

File import instruction

Abstract

Graphic abstract

Glioblastoma (GBM) is a highly vascularized malignant tumor that depends on new blood vessel formation. Small molecules targeting the angiogenic process may be an effective anti-GBM therapeutic strategy. We previously demonstrated that RhoJ promoted the progression and invasion of GBM. RhoJ has also been shown to be expressed in endothelial cells and plays an important role in regulating endothelial cell migration and tumor angiogenesis. Therefore, we aimed to evaluate the role and mechanism of actions of RhoJ in GBM angiogenesis. We analyzed the expression of RhoJ in different grade gliomas and investigated its role in GBM angiogenesis in vivo and in vitro. Furtherly, RNA sequencing (RNA-seq), Western blotting and immunofluorescence were performed to identify the molecular mechanism of RhoJ in regulating endothelial cell behavior and GBM angiogenesis. Here, we found that silencing RhoJ resulted in inhibition of HUVEC cell migration and blood vessel formation. Overexpression of RhoJ promoted the expression of CD31, EpCAM and moesin, suggesting RhoJ facilitated angiogenesis and the malignant progression of GBM. RNA-seq data showed that VEGF/TNF signaling pathway positively regulated RhoJ. The expression levels of RhoJ was upregulated with the stimulation of VEGF, and reduced by the treatment of JNK inhibitor SP600125. It was also found that the activity of PAK-BRAF-ERK was down-regulated upon RhoJ and JNK knockdown. In conclusion, these results suggested that RhoJ plays an essential role in regulating GBM angiogenesis through the JNK/VEGFR2-PAK-ERK signaling pathway and there might exist a VEGF-JNK/ERK-VEGF circuitry. Thus, RhoJ may be a candidate therapeutic target for anti-angiogenesis treatment in GBM.

Keywords: RhoJ, Angiogenesis, GBM, VEGFR2, JNK


Citation styles

APA
Wang, M., Zhang, C., Zheng, Q., Ma, Z., Qi, M., Di, G., Ling, S., Xu, H., Qi, B., Yao, C., Xia, H., Jiang, X. (2022). RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways. International Journal of Biological Sciences, 18(3), 942-955. https://doi.org/10.7150/ijbs.65653.

ACS
Wang, M.; Zhang, C.; Zheng, Q.; Ma, Z.; Qi, M.; Di, G.; Ling, S.; Xu, H.; Qi, B.; Yao, C.; Xia, H.; Jiang, X. RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways. Int. J. Biol. Sci. 2022, 18 (3), 942-955. DOI: 10.7150/ijbs.65653.

NLM
Wang M, Zhang C, Zheng Q, Ma Z, Qi M, Di G, Ling S, Xu H, Qi B, Yao C, Xia H, Jiang X. RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways. Int J Biol Sci 2022; 18(3):942-955. doi:10.7150/ijbs.65653. https://www.ijbs.com/v18p0942.htm

CSE
Wang M, Zhang C, Zheng Q, Ma Z, Qi M, Di G, Ling S, Xu H, Qi B, Yao C, Xia H, Jiang X. 2022. RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways. Int J Biol Sci. 18(3):942-955.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image