Programmed Cell Death Protein 10 (PDCD10) Regulates Vesicle Trafficking and Contributes to the Progression of Clear Cell Renal Cell Carcinoma

IF 14.5 1区 医学 Q1 CELL BIOLOGY
Rui Wang, Tianyu Lin, Yi Liu, Hao Wang, Xinyu Liu, Yihan Dong, Jiaxin Li, Huamao Jiang, Ruibing Chen, Yong Wang, Dan Yue
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引用次数: 0

Abstract

Vesicle trafficking is an essential cellular process that plays an important role in tumour progression. Here, we performed a comprehensive transcriptomic and proteomic analysis on 50 clear cell renal cell carcinoma (ccRCC) tumour samples, and the data systematically depicted the alterations in the molecular landscape. Intriguingly, our investigation uncovered profound dysregulation of the vesicle trafficking process. Particularly, PDCD10 was overexpressed in ccRCC, and functional assays showed that PDCD10 promoted cell proliferation, migration and invasion in vitro and enhanced tumour growth in vivo. Additionally, we identified PDCD10 as a critical regulator of endocytosis and exosome secretion. Proteomic analysis of extracellular vesicles (EVs) suggested that PDCD10 overexpression altered the cargo content in EVs and elevated the abundances of cell adhesion and extracellular matrix molecules. Furthermore, Erlotinib treatment impaired PDCD10-induced endocytosis and suppressed cell proliferation and invasion. Collectively, our findings underscore the significance of PDCD10 as a regulator of vesicle trafficking in ccRCC and a potential target for developing novel anticancer therapeutics.

Abstract Image

程序性细胞死亡蛋白10 (PDCD10)调控囊泡运输并参与透明细胞肾细胞癌的进展
囊泡运输是一个重要的细胞过程,在肿瘤进展中起重要作用。在这里,我们对50个透明细胞肾细胞癌(ccRCC)肿瘤样本进行了全面的转录组学和蛋白质组学分析,数据系统地描述了分子景观的变化。有趣的是,我们的调查揭示了囊泡运输过程的严重失调。特别是,PDCD10在ccRCC中过表达,功能分析显示PDCD10在体外促进细胞增殖、迁移和侵袭,并在体内促进肿瘤生长。此外,我们发现PDCD10是胞吞作用和外泌体分泌的关键调节因子。细胞外囊泡(EVs)的蛋白质组学分析表明,PDCD10过表达改变了EVs中的货物含量,提高了细胞粘附和细胞外基质分子的丰度。此外,厄洛替尼治疗削弱了pdcd10诱导的内吞作用,抑制了细胞的增殖和侵袭。总之,我们的研究结果强调了PDCD10作为ccRCC囊泡运输调节因子的重要性,以及开发新型抗癌疗法的潜在靶点。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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