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Original Article | Open Access

LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma

Yuantong Liu1, Shujin Li1, Shuo Wang1, Qichao Yang1, Zhizhong Wu1, Mengjie Zhang1, Lei Chen1, Zhijun Sun1,2 ( )
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
Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
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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.

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International Journal of Oral Science
Volume 15,
2023
Article number: 24
DOI: 10.1038/s41368-023-00229-0
Cite this article:
Liu Y, Li S, Wang S, et al. LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma. International Journal of Oral Science, 2023, 15: 24. https://doi.org/10.1038/s41368-023-00229-0

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Received: 07 November 2022
Revised: 05 May 2023
Accepted: 12 May 2023
Published: 08 June 2023
© The Author(s) 2023

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