The DOI matches its Crossref record.
Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis
Open accessAbstract
The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis. Although altered Notch signaling has been linked to human diseases, including cancer, evidence for a substantial involvement of Notch in human tumors has remained elusive. Here, we show that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb-positive, tumor cells inhibits proliferation. Increased Notch signaling is observed in Numb-negative tumors, but reverts to basal levels after enforced expression of Numb. Conversely, Numb silencing increases Notch signaling in normal breast cells and in Numb-positive breast tumors. Finally, growth suppression of Numb-negative, but not Numb-positive, breast tumors can be achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological antagonism is relevant to the homeostasis of the normal mammary parenchyma and its subversion contributes to human mammary carcinogenesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Cancer stem cells: an old idea–a paradigm shift
Wicha, M. S., Liu, S., & Dontu, G. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3153 · Cited by 1,378
Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs
Oskarsson, T., Acharyya, S., Zhang, X. H.-F., Vanharanta, S., Tavazoie, S. F., Morris, P. G., Downey, R. J., Manova-Todorova, K., Brogi, E., & Massagué, J. (2011) · Nature Medicine · doi:10.1038/nm.2379 · Cited by 869
Notch signaling mediates hypoxia-induced tumor cell migration and invasion
Sahlgren, C., Gustafsson, M. V., Jin, S., Poellinger, L., & Lendahl, U. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802047105 · Cited by 823
Direct inhibition of the NOTCH transcription factor complex
Moellering, R. E., Cornejo, M., Davis, T. N., Bianco, C. D., Aster, J. C., Blacklow, S. C., Kung, A. L., Gilliland, D. G., Verdine, G. L., & Bradner, J. E. (2009) · Nature · doi:10.1038/nature08543 · Cited by 752
NUMB controls p53 tumour suppressor activity
Colaluca, I. N., Tosoni, D., Nuciforo, P., Senic-Matuglia, F., Galimberti, V., Viale, G., Pece, S., & Di Fiore, P. P. (2008) · Nature · doi:10.1038/nature06412 · Cited by 385
Metadata
- Authors
- Pece, S., Serresi, M., Santolini, E., Capra, M., Hulleman, E., Galimberti, V., Zurrida, S., Maisonneuve, P., Viale, G., & Di Fiore, P. P.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-10-18
- Volume
- 167
- Issue
- 2
- Pages
- 215-221
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2001286107
- Cited by
- 483
- References
- 0
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. https://app.cochat.ai/papers/10.1083/jcb.200406140
- The paper
- Pece, S., Serresi, M., Santolini, E., Capra, M., Hulleman, E., Galimberti, V., Zurrida, S., Maisonneuve, P., Viale, G., & Di Fiore, P. P. (2004). Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200406140
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
