LIM and SH3 protein 1 induces glioma growth and invasion through PI3K/AKT signaling and epithelial-mesenchymal transition - 16/06/19
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Graphical abstract |
Highlights |
• | We further described the role of LASP1 in glioma sustained growth and invasion. |
• | We demonstrated that LASP1 activated the PI3K/AKT pro-survival signaling pathways and induced EMT process by Snail in glioma. |
• | Combiantion of temozolomide and PI3K/AKT revealed enhanced anticancer effects and provides new approach for glioma therapy. |
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : LASP1, Glioma, PI3K/AKT, Snail, EMT
Plan
Vol 116
Article 109013- août 2019 Retour au numéro
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