在头颈部鳞状细胞癌中,LIMP-2通过促进自噬诱导的GSK3β降解增强癌症干样细胞特性。

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-06-08 DOI:10.1038/s41368-023-00229-0
Yuantong Liu, Shujin Li, Shuo Wang, Qichao Yang, Zhizhong Wu, Mengjie Zhang, Lei Chen, Zhijun Sun
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引用次数: 1

摘要

癌症干细胞样细胞(CSCs)具有很强的肿瘤诱发能力和可塑性,在头颈部鳞状细胞癌(HNSCC)的异质性、转移和耐药性中扮演着不可或缺的角色。在这里,我们发现了一个名为 LIMP-2 的候选基因,它是调控 HNSCC 进展和 CSC 特性的新型治疗靶点。LIMP-2 在 HNSCC 患者中的高表达提示其预后较差,并可能对免疫疗法产生抗药性。在功能上,LIMP-2可促进自溶体的形成,从而促进自噬通量。敲除 LIMP-2 可抑制自噬通量,降低 HNSCC 的致瘤能力。进一步的机理研究表明,自噬的增强有助于HNSCC维持干性,促进GSK3β的降解,进而促进β-catenin的核转位和下游靶基因的转录。总之,这项研究揭示了LIMP-2是HNSCC的一个新的前瞻性治疗靶点,并为自噬、CSC和免疫疗法耐药性之间的联系提供了证据。
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LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma.

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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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
期刊最新文献
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