A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer
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...
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| Format: | Article |
| Language: | English |
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Wiley
2024-11-01
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| Series: | Journal of Extracellular Vesicles |
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| Online Access: | https://doi.org/10.1002/jev2.70002 |
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| _version_ | 1846149680271982592 |
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| author | Xiaoyu Wei Mengmeng Liang Min Deng Ji Zheng Fei Luo Qinyu Ma |
| author_facet | Xiaoyu Wei Mengmeng Liang Min Deng Ji Zheng Fei Luo Qinyu Ma |
| author_sort | Xiaoyu Wei |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7a0056aff96d480e83b4c69ceac564be |
| institution | Kabale University |
| issn | 2001-3078 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-7a0056aff96d480e83b4c69ceac564be2024-11-29T11:34:28ZengWileyJournal of Extracellular Vesicles2001-30782024-11-011311n/an/a10.1002/jev2.70002A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancerXiaoyu Wei0Mengmeng Liang1Min Deng2Ji Zheng3Fei Luo4Qinyu Ma5Department of Orthopedics, Southwest Hospital Third Military Medical University Chongqing ChinaDepartment of Orthopedics, Southwest Hospital Third Military Medical University Chongqing ChinaDepartment of Urology Xinqiao Hospital, Third Military Medical University Chongqing ChinaDepartment of Urology Xinqiao Hospital, Third Military Medical University Chongqing ChinaDepartment of Orthopedics, Southwest Hospital Third Military Medical University Chongqing ChinaDepartment of Orthopedics, Southwest Hospital Third Military Medical University Chongqing ChinaAbstract 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.https://doi.org/10.1002/jev2.70002autophagosome‐lysosome fusionbone metastatic nicheextracellular vesiclessecretory autophagytumour‐associated bone remodelling |
| spellingShingle | Xiaoyu Wei Mengmeng Liang Min Deng Ji Zheng Fei Luo Qinyu Ma A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer Journal of Extracellular Vesicles autophagosome‐lysosome fusion bone metastatic niche extracellular vesicles secretory autophagy tumour‐associated bone remodelling |
| title | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer |
| title_full | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer |
| title_fullStr | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer |
| title_full_unstemmed | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer |
| title_short | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer |
| title_sort | switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer |
| topic | autophagosome‐lysosome fusion bone metastatic niche extracellular vesicles secretory autophagy tumour‐associated bone remodelling |
| url | https://doi.org/10.1002/jev2.70002 |
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