Corosolic Acid Attenuates the Invasiveness of Glioblastoma Cells by Promoting CHIP-Mediated AXL Degradation and Inhibiting GAS6/AXL/JAK Axis

doi:10.3390/cells10112919

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23748

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题名:	Corosolic Acid Attenuates the Invasiveness of Glioblastoma Cells by Promoting CHIP-Mediated AXL Degradation and Inhibiting GAS6/AXL/JAK Axis
作者:	Sun, LW;Kao, SH;Yang, SF;Jhang, SW;Lin, YC;Chen, CM;Hsieh, YH
关键词:	corosolic acid;glioblastoma cell;invasiveness;AXL;CHIP;GAS6;JAK2
日期:	2021
上传时间:	2022-08-05T09:42:15Z (UTC)
出版者:	MDPI
摘要:	Corosolic acid (CA), a bioactive compound obtained from Actinidia chinensis, has potential anti-cancer activities. Glioblastoma (GBM) is a malignant brain tumor and whether CA exerts anti-cancer activity on GBM remains unclear. This study was aimed to explore the anticancer activity and its underlying mechanism of CA in GBM cells. Our findings showed that CA & LE; 20 mu M did not affect cell viability and cell proliferative rate of normal astrocyte and four GBM cells. Notably, 10 or 20 mu M CA significantly inhibited cell migration and invasion of three GBM cells, decreased the protein level of F-actin and disrupted F-actin polymerization in these GBM cells. Further investigation revealed that CA decreased AXL level by promoting ubiquitin-mediated proteasome degradation and upregulating the carboxyl terminus of Hsc70-interacting protein (CHIP), an inducer of AXL polyubiquitination. CHIP knock-down restored the CA-reduced AXL and invasiveness of GBM cells. Additionally, we observed that CA-reduced Growth arrest-specific protein 6 (GAS6) and inhibited JAK2/MEK/ERK activation, and GAS6 pre-treatment restored attenuated JAK2/MEK/ERK activation and invasiveness of GBM cells. Furthermore, molecular docking analysis revealed that CA might bind to GAS6 and AXL. These findings collectively indicate that CA attenuates the invasiveness of GBM cells, attributing to CHIP upregulation and binding to GAS6 and AXL and subsequently promoting AXL degradation and downregulating GAS6-mediated JAK2/MEK/ERK cascade. Conclusively, this suggests that CA has potential anti-metastatic activity on GBM cells by targeting the CHIP/GAS6/AXL axis.
URI:	http://dx.doi.org/10.3390/cells10112919 https://www.webofscience.com/wos/woscc/full-record/WOS:000725139800001 https://ir.csmu.edu.tw:8080/handle/310902500/23748
關聯:	CELLS ,2021,v10,issue 11
显示于类别:	[中山醫學大學研究成果] 期刊論文

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