Xiaoxin Sun, Haotian Wu, Ling Tang, Abdullah Al-Danakh, Yuli Jian, Li Gong, Congchen Li, Xiao Yu, Guang Zeng, Qiwei Chen, Deyong Yang, Shujing Wang
{"title":"GALNT6 通过上皮-间充质转化和 CD8+ T 细胞促进膀胱癌恶变和免疫逃逸。","authors":"Xiaoxin Sun, Haotian Wu, Ling Tang, Abdullah Al-Danakh, Yuli Jian, Li Gong, Congchen Li, Xiao Yu, Guang Zeng, Qiwei Chen, Deyong Yang, Shujing Wang","doi":"10.1186/s12935-024-03492-1","DOIUrl":null,"url":null,"abstract":"<p><p>Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8<sup>+</sup> T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382498/pdf/","citationCount":"0","resultStr":"{\"title\":\"GALNT6 promotes bladder cancer malignancy and immune escape by epithelial-mesenchymal transition and CD8<sup>+</sup> T cells.\",\"authors\":\"Xiaoxin Sun, Haotian Wu, Ling Tang, Abdullah Al-Danakh, Yuli Jian, Li Gong, Congchen Li, Xiao Yu, Guang Zeng, Qiwei Chen, Deyong Yang, Shujing Wang\",\"doi\":\"10.1186/s12935-024-03492-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8<sup>+</sup> T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382498/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-024-03492-1\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-024-03492-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
膀胱癌(BC)是男性第六大癌症,也是全球第九大常见癌症。传统的治疗方式,包括手术、放疗、化疗和免疫疗法,在某些晚期病例中疗效有限。GALNT6介导的异常O-糖基化修饰参与多种恶性肿瘤和免疫逃避是一个猜测的主题。然而,其在 BC 中的重要性尚未得到研究。通过整合生物信息学分析和实验室实验,我们成功地阐明了 GALNT6 在 BC 中的作用。我们的研究发现,GALNT6在BC中有显著表达,其高水平表达与晚期和高分级相关,导致总生存率低下。此外,体外和体内实验均表明,GALNT6 水平的升高与肿瘤的生长、迁移和侵袭密切相关。此外,GALNT6 水平的升高、肿瘤微环境中 CD8+ T 细胞的浸润程度与患者的预后呈负相关。功能实验表明,GALNT6 表达的增加可通过激活上皮-间质转化(EMT)途径增强癌细胞的恶性特征。简而言之,本研究探讨了 GALNT6 介导的异常 O 型糖基化对膀胱癌发生和发展的影响,以及其对免疫逃避的影响。研究还探讨了肿瘤细胞与免疫细胞之间相互作用的可能分子机制,以及其中涉及的双向信号转导。这些发现为免疫疗法在膀胱癌中的临床应用提供了植根于糖生物学的新理论基础。
GALNT6 promotes bladder cancer malignancy and immune escape by epithelial-mesenchymal transition and CD8+ T cells.
Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8+ T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC.
期刊介绍:
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.