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Plexin-B1 indirectly affects glioma invasiveness and angiogenesis by regulating the RhoA/αvβ3 signaling pathway and SRPK1

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Tumor Biology

Abstract

Gliomas are one of the most common primary brain tumors in adults. They display aggressive invasiveness, are highly vascular, and have a poor prognosis. Plexin-B1 is involved in numerous cellular processes, especially cellular migration and angiogenesis. However, the role and regulatory mechanisms of Plexin-B1 in gliomas are not understood and were thus investigated in this study. By using multiple and diverse experimental techniques, we investigated cell apoptosis, mitochondrial membrane potential, cell migration and invasion, angiogenesis, PI3K and Akt phosphorylation, and also the levels of SRPK1 and αvβ3 in glioma cells and animal glioma tissues. The results indicated that Plexin-B1 expression in glioma cell lines is increased compared to normal human astrocytes. Plexin-B1 mediates RhoA/integrin αvβ3 involved in the PI3K/Akt pathway and SRPK1 to influence the growth of glioma cell, angiogenesis, and motility in vitro and in vivo. Thus, Plexin-B1 signaling regulates the Rho/αvβ3/PI3K/Akt pathway and SRPK1, which are involved in glioma invasiveness and angiogenesis. Therefore, the new drug research should focus on Plexin-B1 as a target for the treatment of glioma invasion and angiogenesis.

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Acknowledgments

This study was supported, in part, by the Key Project of the National Natural Science Foundation of Shandong Province (ZR 2009CL004), the China Postdoctoral Science Foundation (20100481466), the Foundation of Taishan Scholar (tshw20110575), the Pharmaceutical Health Science and Technology Development Program of Shandong Province (2011QZ001, 2013G0021816), the National Natural Science Foundation of China (81171142/H0910, 81271092, 61427807), a Project of the Shandong Province Higher Educational Science and Technology Program (J11LF61), and the Program of Major Research and Development Institutions in Fujian Province (2012I2014).

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Authors and Affiliations

  1. Institute of Human Anatomy and Histology and Embryology, Otology & Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Laishan District, Shandong Province, 264003, China

    Yingwei Chang, Li Li, Luping Zhang, Xuyan Guo, Zhuoying Feng, Junchen Zhou, Shuai Zhou, Guoying Feng, Fengchan Han & Fei Huang

  2. Neurosurgery, Binzhou Medical University Yantai Affiliated Hospital, 629 Nanhua Road, Muping Area, Shandong Province, 264003, China

    Jun Yang

  3. Institute of Human Anatomy and Histology and Embryology, Southern Medical University, 1023 Shatainan Road, Baiyun District, Guangzhou, 510515, China

    Wenhua Huang

  4. Qingdao Economic and Technological Development Area First People’s Hospital, Qingdao, China

    Yingwei Chang

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  1. Yingwei Chang
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  2. Li Li
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  11. Jun Yang
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Correspondence to Jun Yang or Fei Huang.

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Yingwei Chang and Li Li contributed to this work equally and should be considered as co-first authors

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Chang, Y., Li, L., Zhang, L. et al. Plexin-B1 indirectly affects glioma invasiveness and angiogenesis by regulating the RhoA/αvβ3 signaling pathway and SRPK1. Tumor Biol. 37, 11225–11236 (2016). https://doi.org/10.1007/s13277-016-4849-9

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  • DOI: https://doi.org/10.1007/s13277-016-4849-9

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