A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer

IF 15.5 1区 医学 Q1 CELL BIOLOGY Journal of Extracellular Vesicles Pub Date : 2024-11-05 DOI:10.1002/jev2.70002
Xiaoyu Wei, Mengmeng Liang, Min Deng, Ji Zheng, Fei Luo, Qinyu Ma
{"title":"A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer","authors":"Xiaoyu Wei,&nbsp;Mengmeng Liang,&nbsp;Min Deng,&nbsp;Ji Zheng,&nbsp;Fei Luo,&nbsp;Qinyu Ma","doi":"10.1002/jev2.70002","DOIUrl":null,"url":null,"abstract":"<p>The identification of both autophagy-related material degradation and unconventional secretion has paved the way for significant breakthroughs linking autophagy to a plethora of physiological processes and disease conditions. However, the mechanisms that coordinate these two pathways remain elusive. Here, we demonstrate that a switch from the lysosomal degradation to a secretory autophagy pathway is governed by protein tyrosine phosphatase 1B (PTP1B, encoded by <i>PTPN1</i>). Dephosphorylation at two tyrosine residues of syntaxin17 (STX17) by PTP1B reduces autophagosome-lysosome fusion while switching the cells to a secretory autophagy pathway. Both PTP1B overexpression and tumour-derived extracellular vesicles (EVs) can activate the secretory autophagy pathway in osteoblasts. Moreover, we demonstrate that osteoblastic LC3+ EVs, generated via the secretory autophagy pathway, are the primary contributor to tumour-associated bone remodelling in prostate cancer. Depletion of tumour-derived EVs secretion or genetic ablation of osteoblastic PTP1B rescues aberrant bone remodelling and lesions, highlighting the relevance between LC3+ EVs and the formation of bone metastatic niche. Our results reveal the significance of tumour-regulated PTP1B in the fate decision of autophagosomes, and propose a role ofLC3+ EVs in shaping the bone metastatic niche.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 11","pages":""},"PeriodicalIF":15.5000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70002","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Extracellular Vesicles","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jev2.70002","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The identification of both autophagy-related material degradation and unconventional secretion has paved the way for significant breakthroughs linking autophagy to a plethora of physiological processes and disease conditions. However, the mechanisms that coordinate these two pathways remain elusive. Here, we demonstrate that a switch from the lysosomal degradation to a secretory autophagy pathway is governed by protein tyrosine phosphatase 1B (PTP1B, encoded by PTPN1). Dephosphorylation at two tyrosine residues of syntaxin17 (STX17) by PTP1B reduces autophagosome-lysosome fusion while switching the cells to a secretory autophagy pathway. Both PTP1B overexpression and tumour-derived extracellular vesicles (EVs) can activate the secretory autophagy pathway in osteoblasts. Moreover, we demonstrate that osteoblastic LC3+ EVs, generated via the secretory autophagy pathway, are the primary contributor to tumour-associated bone remodelling in prostate cancer. Depletion of tumour-derived EVs secretion or genetic ablation of osteoblastic PTP1B rescues aberrant bone remodelling and lesions, highlighting the relevance between LC3+ EVs and the formation of bone metastatic niche. Our results reveal the significance of tumour-regulated PTP1B in the fate decision of autophagosomes, and propose a role ofLC3+ EVs in shaping the bone metastatic niche.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
从溶酶体降解到分泌型自噬的转换启动了前列腺癌的成骨性骨转移。
自噬相关物质降解和非常规分泌的发现,为自噬与大量生理过程和疾病相关的重大突破铺平了道路。然而,协调这两种途径的机制仍然难以捉摸。在这里,我们证明了从溶酶体降解到分泌型自噬途径的转换是由蛋白酪氨酸磷酸酶 1B (PTP1B,由 PTPN1 编码)控制的。PTP1B使syntaxin17(STX17)的两个酪氨酸残基去磷酸化会减少自噬体与溶酶体的融合,同时使细胞转向分泌型自噬途径。PTP1B过表达和肿瘤衍生的细胞外囊泡(EVs)都能激活成骨细胞的分泌性自噬途径。此外,我们还证明了通过分泌性自噬途径产生的成骨细胞 LC3+ EVs 是前列腺癌肿瘤相关骨重塑的主要因素。消耗肿瘤衍生的EVs分泌或基因消减成骨细胞的PTP1B可挽救异常的骨重塑和病变,这突出了LC3+ EVs与骨转移龛形成之间的相关性。我们的研究结果揭示了肿瘤调控的 PTP1B 在自噬体命运决定中的重要作用,并提出了 LC3+ EVs 在形成骨转移龛中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
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.
期刊最新文献
Extracellular vesicles containing SARS-CoV-2 proteins are associated with multi-organ dysfunction and worse outcomes in patients with severe COVID-19 Efficient enzyme-free isolation of brain-derived extracellular vesicles Hypoxia and TNF-alpha modulate extracellular vesicle release from human induced pluripotent stem cell-derived cardiomyocytes PlexinA1 (PLXNA1) as a novel scaffold protein for the engineering of extracellular vesicles A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1