期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01556-7
关键词
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资金
- Burroughs Wellcome Fund Career Award at the Scientific Interface [1012027]
- NSF CAREER Award [1651855]
- UCSD CTRI grant
- FISP grant
- AIM pilot grant
- NIH [DP5-OD017937]
- UCSD FISP grant
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1651855] Funding Source: National Science Foundation
- Div Of Engineering Education and Centers
- Directorate For Engineering [1559781] Funding Source: National Science Foundation
The topographical organization of collagen within the tumor microenvironment has been implicated in modulating cancer cell migration and independently predicts progression to metastasis. Here, we show that collagen matrices with small pores and short fibers, but not Matrigel, trigger a conserved transcriptional response and subsequent motility switch in cancer cells resulting in the formation of multicellular network structures. The response is not mediated by hypoxia, matrix stiffness, or bulk matrix density, but rather by matrix architecture-induced beta 1-integrin upregulation. The transcriptional module associated with network formation is enriched for migration and vasculogenesis-associated genes that predict survival in patient data across nine distinct tumor types. Evidence of this gene module at the protein level is found in patient tumor slices displaying a vasculogenic mimicry (VM) phenotype. Our findings link a collagen-induced migration program to VM and suggest that this process may be broadly relevant to metastatic progression in solid human cancers.
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