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Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling
Open accessAbstract
Metastasis is responsible for most cancer deaths. Here, we show that Aes (or Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes was decreased in liver metastases compared with primary colon tumors in both mice and humans. Aes inhibited Notch signaling by converting active Rbpj transcription complexes into repression complexes on insoluble nuclear matrix. In tumor cells, Notch signaling was triggered by ligands on adjoining blood vessels, and stimulated transendothelial migration. Genetic depletion of Aes in Apc(Δ716) intestinal polyposis mice caused marked tumor invasion and intravasation that were suppressed by Notch signaling inhibition. These results suggest that inhibition of Notch signaling can be a promising strategy for prevention and treatment of colon cancer metastasis.
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Citations
Cites
The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited
Fidler, I. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1098 · Cited by 4,686 · cited 1×
“The invasionmetastasis cascade consists of local invasion, intravasation, transport, extravasation, formation of micrometastases, and colonization (Fidler, 2003; Steeg, 2006).”
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Cited by
Tumor Metastasis: Molecular Insights and Evolving Paradigms
Valastyan, S., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.024 · Cited by 4,011
Notch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,114
Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation
Calon, A., Espinet, E., Palomo-Ponce, S., Tauriello, D. V. F., Iglesias, M., Céspedes, M. V., Sevillano, M., Nadal, C., Jung, P., Zhang, X. H.-F., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.08.013 · Cited by 1,060
Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets
Liang, Y., Zhang, H., Song, X., & Yang, Q. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.012 · Cited by 992
Crossing the endothelial barrier during metastasis
Reymond, N., d'Água, B. B., & Ridley, A. J. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3628 · Cited by 922
Metadata
- Authors
- Sonoshita, M., Aoki, M., Fuwa, H., Aoki, K., Hosogi, H., Sakai, Y., Hashida, H., Takabayashi, A., Sasaki, M., Robine, S., Itoh, K., Yoshioka, K., Kakizaki, F., Kitamura, T., Oshima, M., & Taketo, M. M.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 19
- Issue
- 1
- Pages
- 125-137
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2133176657
- Cited by
- 209
- References
- 1
- FWCI
- 8.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sonoshita, M., Aoki, M., Fuwa, H., Aoki, K., Hosogi, H., Sakai, Y., Hashida, H., Takabayashi, A., Sasaki, M., Robine, S., Itoh, K., Yoshioka, K., Kakizaki, F., Kitamura, T., Oshima, M., & Taketo, M. M. (2011). Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling. Cancer Cell. https://doi.org/10.1016/j.ccr.2010.11.008
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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