Bibliographic Details
| Title: |
Cancer cells sense solid stress to enhance metastasis by CKAP4 phase separation-mediated microtubule branching |
| Authors: |
Xing Sun, Yangyang Zhou, Shengjie Sun, Siyuan Qiu, Menglan Peng, Han Gong, Junxiao Guo, Chengcai Wen, Yibin Zhang, Yifang Xie, Hui Li, Long Liang, Guoyan Luo, Wencan Wu, Jing Liu, Weihong Tan, Mao Ye |
| Source: |
Cell Discovery, Vol 10, Iss 1, Pp 1-17 (2024) |
| Publisher Information: |
Nature Publishing Group, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
Abstract Solid stress, originating from rigid and elastic components of extracellular matrix and cells, is a typical physical hallmark of tumors. Mounting evidence indicates that elevated solid stress drives metastasis and affects prognosis. However, the molecular mechanism of how cancer cells sense solid stress, thereby exacerbating malignancy, remains elusive. In this study, our clinical data suggest that elevated stress in metastatic solid tumors is highly associated with the expression of cytoskeleton-associated protein 4 (CKAP4). Intriguingly, CKAP4, as a sensitive intracellular mechanosensor, responds specifically to solid stress in a subset of studied tumor micro-environmental elements through liquid–liquid phase separation. These micron-scaled CKAP4 puncta adhere tightly onto microtubules and dramatically reorchestrate their curvature and branching to enhance cell spreading, which, as a result, boosts cancer cell motility and facilitates distant metastasis in vivo. Mechanistically, the intrinsically disordered region 1 (IDR1) of CKAP4 binds to microtubules, while IDR2 governs phase separation due to the Cav1.2-dependent calcium influx, which collectively remodels microtubules. These findings reveal an unprecedented mechanism of how cancer cells sense solid stress for cancer malignancy and bridge the gap between cancer physics and cancer cell biology. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2056-5968 |
| Relation: |
https://doaj.org/toc/2056-5968 |
| DOI: |
10.1038/s41421-024-00737-1 |
| Access URL: |
https://doaj.org/article/d582fd94c3034b45aead8efaecaefd49 |
| Accession Number: |
edsdoj.582fd94c3034b45aead8efaecaefd49 |
| Database: |
Directory of Open Access Journals |
