LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma
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 thera...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-06-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-023-00229-0 |
| _version_ | 1797806837747154944 |
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| author | Yuantong Liu Shujin Li Shuo Wang Qichao Yang Zhizhong Wu Mengjie Zhang Lei Chen Zhijun Sun |
| author_facet | Yuantong Liu Shujin Li Shuo Wang Qichao Yang Zhizhong Wu Mengjie Zhang Lei Chen Zhijun Sun |
| author_sort | Yuantong Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:13:25Z |
| format | Article |
| id | doaj.art-4204008f7fbb404ebb84502130486496 |
| institution | Directory Open Access Journal |
| issn | 2049-3169 |
| language | English |
| last_indexed | 2024-03-13T06:13:25Z |
| publishDate | 2023-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj.art-4204008f7fbb404ebb845021304864962023-06-11T11:07:12ZengNature Publishing GroupInternational Journal of Oral Science2049-31692023-06-0115111410.1038/s41368-023-00229-0LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinomaYuantong Liu0Shujin Li1Shuo Wang2Qichao Yang3Zhizhong Wu4Mengjie Zhang5Lei Chen6Zhijun Sun7The 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 UniversityThe 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 UniversityThe 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 UniversityThe 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 UniversityThe 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 UniversityThe 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 UniversityThe 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 UniversityThe 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 UniversityAbstract 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.https://doi.org/10.1038/s41368-023-00229-0 |
| spellingShingle | Yuantong Liu Shujin Li Shuo Wang Qichao Yang Zhizhong Wu Mengjie Zhang Lei Chen Zhijun Sun 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 |
| title | LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma |
| title_full | LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma |
| title_fullStr | LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma |
| title_full_unstemmed | LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma |
| title_short | LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma |
| title_sort | limp 2 enhances cancer stem like cell properties by promoting autophagy induced gsk3β degradation in head and neck squamous cell carcinoma |
| url | https://doi.org/10.1038/s41368-023-00229-0 |
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