Elucidation of CKAP4-remodeled cell mechanics in driving metastasis of bladder cancer through aptamer-based target discovery
Metastasis contributes to the dismal prognosis of bladder cancer (BLCA). The mechanical status of the cell membrane is expected to mirror the ability of cell migration to promote cancer metastasis. However, the mechanical characteristics and underlying molecular profile associated with BLCA metastasis remain obscure. To study the unique cellular architecture and traits associated with cell migration, using a process called cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) we generated an aptamer-based molecular probe, termed spl3c, which identified cytoskeleton-associated protein 4 (CKAP4). CKAP4 was associated with tumor metastasis in BLCA, but we also found it to be a mechanical regulator of BLCA cells through the maintenance of a central-to-peripheral gradient of stiffness on the cell membrane. Notably, such mechanical traits were transportable through exosome-mediated intercellular CKAP4 trafficking, leading to significant enhancement of migration in recipient cells and, consequently, aggravating metastatic potential in vivo. Taken together, our study shows the robustness of this aptamer-based molecular tool for biomarker discovery, revealing the dominance of a CKAP4-induced central-to-peripheral gradient of membrane stiffness that benefits cell migration and delineating the role of exosomes in mediating mechanical signaling in BLCA metastasis.
| Errataetall: |
CommentIn: J Urol. 2022 Dec;208(6):1340-1342. - PMID 36154669 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 119(2022), 16 vom: 19. Apr., Seite e2110500119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Xing [VerfasserIn] |
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| Links: |
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| Themen: |
Aptamer |
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| Anmerkungen: |
Date Completed 14.04.2022 Date Revised 10.11.2022 published: Print-Electronic CommentIn: J Urol. 2022 Dec;208(6):1340-1342. - PMID 36154669 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2110500119 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Metastasis contributes to the dismal prognosis of bladder cancer (BLCA). The mechanical status of the cell membrane is expected to mirror the ability of cell migration to promote cancer metastasis. However, the mechanical characteristics and underlying molecular profile associated with BLCA metastasis remain obscure. To study the unique cellular architecture and traits associated with cell migration, using a process called cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) we generated an aptamer-based molecular probe, termed spl3c, which identified cytoskeleton-associated protein 4 (CKAP4). CKAP4 was associated with tumor metastasis in BLCA, but we also found it to be a mechanical regulator of BLCA cells through the maintenance of a central-to-peripheral gradient of stiffness on the cell membrane. Notably, such mechanical traits were transportable through exosome-mediated intercellular CKAP4 trafficking, leading to significant enhancement of migration in recipient cells and, consequently, aggravating metastatic potential in vivo. Taken together, our study shows the robustness of this aptamer-based molecular tool for biomarker discovery, revealing the dominance of a CKAP4-induced central-to-peripheral gradient of membrane stiffness that benefits cell migration and delineating the role of exosomes in mediating mechanical signaling in BLCA metastasis | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Xie, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yangyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yibin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Tiantian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yinglei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zilong |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Tianhuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Wencan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Mao |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Weihong |e verfasserin |4 aut | |
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