The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts
Open accessAbstract
Carcinoma-associated fibroblasts (CAF) mediate the onset of a proinvasive tumour microenvironment. The proinflammatory cytokine LIF reprograms fibroblasts into a proinvasive phenotype, which promotes extracellular matrix remodelling and collective invasion of cancer cells. Here we unveil that exposure to LIF initiates an epigenetic switch leading to the constitutive activation of JAK1/STAT3 signalling, which results in sustained proinvasive activity of CAF. Mechanistically, p300-histone acetyltransferase acetylates STAT3, which, in turn, upregulates and activates the DNMT3b DNA methyltransferase. DNMT3b methylates CpG sites of the SHP-1 phosphatase promoter, which abrogates SHP-1 expression, and results in constitutive phosphorylation of JAK1. Sustained JAK1/STAT3 signalling is maintained by DNA methyltransferase DNMT1. Consistently, in human lung and head and neck carcinomas, STAT3 acetylation and phosphorylation are inversely correlated with SHP-1 expression. Combined inhibition of DNMT activities and JAK signalling, in vitro and in vivo, results in long-term reversion of CAF-associated proinvasive activity and restoration of the wild-type fibroblast phenotype.
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Cites
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Cited by
The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366
A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863
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Biffi, G., Oni, T. E., Spielman, B., Hao, Y., Elyada, E., Park, Y., Preall, J., & Tuveson, D. A. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0710 · Cited by 1,360
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265
Metadata
- Authors
- Albrengues, J., Bertero, T., Grasset, E., Bonan, S., Maiel, M., Bourget, I., Philippe, C., Herraiz Serrano, C., Benamar, S., Croce, O., Sanz-Moreno, V., Meneguzzi, G., Feral, C. C., Cristofari, G., & Gaggioli, C.
- Venue
- Nature Communications
- Published
- 2015-12-15
- Volume
- 6
- Issue
- 1
- Pages
- 10204-10204
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2263390674
- Cited by
- 367
- References
- 61
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- gold
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- Albrengues, J., Bertero, T., Grasset, E., Bonan, S., Maiel, M., Bourget, I., Philippe, C., Herraiz Serrano, C., Benamar, S., Croce, O., Sanz-Moreno, V., Meneguzzi, G., Feral, C. C., Cristofari, G., & Gaggioli, C. (2015). Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts. Nature Communications. https://doi.org/10.1038/ncomms10204
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