Elucidation of CKAP4-remodeled cell mechanics in driving metastasis of bladder cancer through aptamer-based target discovery.
Elucidation of CKAP4-remodeled cell mechanics in driving metastasis of bladder cancer through aptamer-based target discovery.
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通过基于适体的靶标发现阐明 CKAP4 重塑的细胞力学驱动膀胱癌转移
DOI：
10.1073/pnas.2110500119
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发表时间：
2022-04-19
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
Metastasis generally leads to a dismal prognosis in bladder cancer (BLCA). The mechanical status of the cell membrane has been reported to reflect the potential of the metastatic capacity of cancer cells. However, the molecular profile and corresponding mechanical traits underlying BLCA metastasis remain largely elusive. Our study demonstrates the significance of cytoskeleton-associated protein 4 (CKAP4) in BLCA malignancy through aptamer selection, emphasizes the mechanical dominance of the central-to-peripheral gradient over simply softening or stiffening in cell migration, and shows the role of exosomes in mediating mechanical signaling in BLCA metastasis. Altogether, our work verifies the promising advantages of an aptamer-based approach in cancer research, which ranges from biomarker discovery to the elucidation of biological functions. 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.
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影响因子：
19
作者：
Diz-Muñoz A;Fletcher DA;Weiner OD
通讯作者：
Weiner OD
影响因子：
4
作者：
Schaefer, Antje;te Riet, Joost;Hordijk, Peter L.
通讯作者：
Hordijk, Peter L.
影响因子：
7.8
作者：
Raucher, D;Sheetz, M P
通讯作者：
Sheetz, M P
影响因子：
9.7
作者：
Panzetta, Valeria;Musella, Ida;Fusco, Sabato
通讯作者：
Fusco, Sabato
影响因子：
4
作者：
Dillekas, Hanna;Rogers, Michael S.;Straume, Oddhjorn
通讯作者：
Straume, Oddhjorn