A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer
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| Format: | Artículo Open Access |
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Wiley
2024
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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 Xiaoyu Wei Mengmeng Liang Min Deng Ji Zheng Fei Luo Qinyu Ma |
| collection | Wiley Open Access |
| contents | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer Xiaoyu Wei Mengmeng Liang Min Deng Ji Zheng Fei Luo Qinyu Ma Journal of Extracellular Vesicles 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. 10.1002/jev2.70002 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1002/jev2.70002 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_jev2_70002 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer Xiaoyu Wei Mengmeng Liang Min Deng Ji Zheng Fei Luo Qinyu Ma Journal of Extracellular Vesicles A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer Xiaoyu Wei Mengmeng Liang Min Deng Ji Zheng Fei Luo Qinyu Ma Journal of Extracellular Vesicles 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. 10.1002/jev2.70002 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | A switch from lysosomal degradation to secretory autophagy initiates osteogenic bone metastasis in prostate cancer |
| topic | Journal of Extracellular Vesicles |
| url | https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.70002 |