AMPK通过抑制NF-κB激活来减弱SHH亚组髓母细胞瘤的生长和转移。

AMPK attenuates SHH subgroup medulloblastoma growth and metastasis by inhibiting NF-κB activation.

作者信息

Cai Jing, Wang Yue, Wang Xinfa, Ai Zihe, Li Tianyuan, Pu Xiaohong, Yang Xin, Yao Yixing, He Junping, Cheng Steven Y, Yu Tingting, Liu Chen, Yue Shen

机构信息

Department of Medical Genetics, Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China.

Department of Neurosurgery, Children's Hospital of Nanjing Medical University, Nanjing, 210093, China.

出版信息

Cell Biosci. 2023 Jan 22;13(1):15. doi: 10.1186/s13578-023-00963-2.

BACKGROUND

Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Metastasis and relapse are the leading causes of death in MB patients. The initiation of the SHH subgroup of MB (SHH-MB) is due to the aberrant activation of Sonic Hedgehog (Shh) signaling. However, the mechanisms for its metastasis are still unknown.

RESULTS

AMP-dependent protein kinase (AMPK) restrains the activation of Shh signaling pathway, thereby impeding the proliferation of SHH-MB cells. More importantly, AMPK also hinders the growth and metastasis of SHH-MB cells by regulating NF-κB signaling pathway. Furthermore, Vismodegib and TPCA-1, which block the Shh and NF-κB pathways, respectively, synergistically restrained the growth, migration, and invasion of SHH-MB cells.

CONCLUSIONS

This work demonstrates that AMPK functions through two signaling pathways, SHH-GLI1 and NF-κB. AMPK-NF-κB axis is a potential target for molecular therapy of SHH-MB, and the combinational blockade of NF-κB and Shh pathways confers synergy for SHH-MB therapy.