LIM and SH3 protein 1 induces glioma growth and invasion through PI3K/AKT signaling and epithelial-mesenchymal transition

Biomedicine & Pharmacotherapy

Xiangguo Xia¹  Lilei Peng¹  Xianglong Li¹  Xiaobo Yang²  Chuanhong Zhong²  Bei Tao²  Ligang Chen²  Tangming Peng³ 

[1] Neurosurgical Clinical Research Center of Sichuan Province, Luzhou, China;Neurosurgery Department, Affiliated Hospital of Southwest Medical University, Luzhou, China;Rheumatism Department, Affiliated Hospital of Southwest Medical University, Luzhou, China;

关键词: LASP1;    Glioma;    PI3K/AKT;    Snail;    EMT;   

DOI  :  

来源: DOAJ

【 摘 要 】

Purpose: This study investigated the underlying mechanism of LIM and SH3 protein 1 (LASP1)-induced malignant glioma growth and invasion. Materials and methods: We compared the expression of LASP1 in malignant glioma tumor tissues and low-grade glioma tissues by immunohistochemistry. We also compared LASP1 overexpression and LASP1 knockout glioma cell proliferation and invasion in vitro and in vivo. We detected activation of the PI3K/AKT signaling pathway and epithelial-mesenchymal transition (EMT) process in tumor cells by western blotting or immunofluorescence. Glioma-bearing mice were used to investigate the anticancer effects of PI3K/AKT inhibitors in combination with temozolomide. Results: We observed the enhanced expression of LASP1 in malignant glioma tumor tissues compared to low-grade glioma tissues, and LASP1 overexpression in glioma cells revealed an elevated capability of proliferation and invasion in vitro and in vivo. LASP1 overexpression also facilitated PI3K/AKT signaling and the EMT process through the downstream transcription factor Snail, which resulted in the intensive invasion of cancer cells. We combined PI3K/AKT inhibitors and temozolomide to block the LASP1/PI3K/AKT/Snail signaling pathway, which dramatically enhanced tumor suppression and provides an innovative approach for clinical glioma treatment. Conclusion: LASP1 is upregulated in malignant glioma and facilitates glioma cell proliferation and invasion by activation the PI3K/AKT/Snail signaling pathway. Blockade of the PI3K/AKT signal efficiently enhanced the anticancer effects of chemotherapeutic agents, which provides an innovative target in glioma treatment.

【 授权许可】

Unknown