LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma.
10.1038/s41368-023-00229-0
- Author:
Yuantong LIU
1
;
Shujin LI
1
;
Shuo WANG
1
;
Qichao YANG
1
;
Zhizhong WU
1
;
Mengjie ZHANG
1
;
Lei CHEN
1
;
Zhijun SUN
2
Author Information
1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
2. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. sunzj@whu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Autophagy;
Carcinoma, Squamous Cell/pathology*;
Cell Line, Tumor;
Glycogen Synthase Kinase 3 beta/metabolism*;
Head and Neck Neoplasms/pathology*;
Neoplastic Stem Cells/pathology*;
Squamous Cell Carcinoma of Head and Neck/pathology*;
Lysosome-Associated Membrane Glycoproteins
- From:
International Journal of Oral Science
2023;15(1):24-24
- CountryChina
- Language:English
-
Abstract:
Cancer stem cell-like cells (CSCs) play an integral role in the heterogeneity, metastasis, and treatment resistance of head and neck squamous cell carcinoma (HNSCC) due to their high tumor initiation capacity and plasticity. Here, we identified a candidate gene named LIMP-2 as a novel therapeutic target regulating HNSCC progression and CSC properties. The high expression of LIMP-2 in HNSCC patients suggested a poor prognosis and potential immunotherapy resistance. Functionally, LIMP-2 can facilitate autolysosome formation to promote autophagic flux. LIMP-2 knockdown inhibits autophagic flux and reduces the tumorigenic ability of HNSCC. Further mechanistic studies suggest that enhanced autophagy helps HNSCC maintain stemness and promotes degradation of GSK3β, which in turn facilitates nuclear translocation of β-catenin and transcription of downstream target genes. In conclusion, this study reveals LIMP-2 as a novel prospective therapeutic target for HNSCC and provides evidence for a link between autophagy, CSC, and immunotherapy resistance.
