The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Zeb1 links epithelial-mesenchymal transition and cellular senescence
Open accessAbstract
Overexpression of zinc finger E-box binding homeobox transcription factor 1(Zeb1) in cancer leads to epithelial-to-mesenchymal transition (EMT) and increased metastasis. As opposed to overexpression, we show that mutation of Zeb1 in mice causes a mesenchymal-epithelial transition in gene expression characterized by ectopic expression of epithelial genes such as E-cadherin and loss of expression of mesenchymal genes such as vimentin. In contrast to rapid proliferation in cancer cells where Zeb1 is overexpressed,this mesenchymal-epithelial transition in mutant mice is associated with diminished proliferation of progenitor cells at sites of developmental defects, including the forming palate, skeleton and CNS. Zeb1dosage-dependent deregulation of epithelial and mesenchymal genes extends to mouse embryonic fibroblasts (MEFs), and mutant MEFs also display diminished replicative capacity in culture, leading to premature senescence. Replicative senescence in MEFs is classically triggered by products of the Ink4a(Cdkn2a) gene. However, this Ink4a pathway is not activated during senescence of Zeb1 mutant MEFs. Instead, there is ectopic expression of two other cell cycle inhibitory cyclin-dependent kinase inhibitors,p15Ink4b (Cdkn2b) and p21Cdkn1a (Cdkn1a). We demonstrate that this ectopic expression of p15Ink4b extends in vivo to sites of diminished progenitor cell proliferation and developmental defects in Zeb1-null mice.
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
Cites
Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?
Peinado, H., Olmeda, D., & Cano, A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2131 · Cited by 3,121
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
Lessard, J., & Sauvageau, G. (2003) · Nature · doi:10.1038/nature01572 · Cited by 1,452
Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
Molofsky, A. V., Slutsky, S. G., Joseph, N. M., He, S., Pardal, R., Krishnamurthy, J., Sharpless, N. E., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature05091 · Cited by 972
Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all
Gil, J., & Peters, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1987 · Cited by 843
Tumor suppression by Ink4a-Arf: progress and puzzles.
Lowe, S. W., & Sherr, C. J. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00013-8 · Cited by 699 · cited 2×
“It is of note that normal replicative senescence of wild-type MEFs results from time-dependent induction of the Ink4a locus in culture (usually leading to senescence around P10-12) (Lowe and Sherr, 2003; Gil and Peters, 2006).”
BackgroundResultLingbeek, M. E., Jacobs, J. J. L., & van Lohuizen, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200403200 · Cited by 160
Cited by
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931
Brabletz, T., Kalluri, R., Nieto, M. A., & Weinberg, R. A. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.118 · Cited by 1,961
The Ins and Outs of the Epithelial to Mesenchymal Transition in Health and Disease
Nieto, M. A. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154036 · Cited by 720
A MicroRNA Targeting Dicer for Metastasis Control
Martello, G., Rosato, A., Ferrari, F., Manfrin, A., Cordenonsi, M., Dupont, S., Enzo, E., Guzzardo, V., Rondina, M., Spruce, T., et al. (2010) · Cell · doi:10.1016/j.cell.2010.05.017 · Cited by 667
To differentiate or not — routes towards metastasis
Brabletz, T. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3265 · Cited by 623
ZEB1: At the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance
Zhang, P., Sun, Y., & Ma, L. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1006048 · Cited by 611
Anders, L., Ke, N., Hydbring, P., Choi, Y. J., Widlund, H. R., Chick, J. M., Zhai, H., Vidal, M., Gygi, S. P., Braun, P., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.10.001 · Cited by 543
EMT as the ultimate survival mechanism of cancer cells
Tiwari, N., Gheldof, A., Tatari, M., & Christofori, G. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.02.013 · Cited by 512
ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1
Zhang, P., Wei, Y., Wang, L., Debeb, B. G., Yuan, Y., Zhang, J., Yuan, J., Wang, M., Chen, D., Sun, Y., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3013 · Cited by 454
Self-citationThe Transcriptional Corepressor CtBP: A Foe of Multiple Tumor Suppressors
Chinnadurai, G. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3349 · Cited by 264
Epigenomic dissection of Alzheimer’s disease pinpoints causal variants and reveals epigenome erosion
Xiong, X., James, B. T., Boix, C. A., Park, Y. P., Galani, K., Victor, M. B., Sun, N., Hou, L., Ho, L.-L., Mantero, J., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.040 · Cited by 205
CellOracle: Dissecting cell identity via network inference and in silico gene perturbation
Kamimoto, K., Hoffmann, C. M., & Morris, S. A. (2020) · doi:10.1101/2020.02.17.947416 · Cited by 81
Vazquez-Martin, A., López-Bonetc, E., Cufí, S., Oliveras-Ferraros, C., Del Barco, S., Martin-Castillo, B., & Menendez, J. A. (2011) · Drug Resistance Updates · doi:10.1016/j.drup.2011.04.003 · Cited by 66
RAP80 regulates epithelial–mesenchymal transition related with metastasis and malignancy of cancer
Park, S. Y., Korm, S., Chung, H. J., Choi, S. J., Jang, J., Cho, S., Lim, Y. T., Kim, H., & Lee, J. (2016) · Cancer Science · doi:10.1111/cas.12877 · Cited by 12
Establishing the relationship between brain cellular senescence and brain structure
Lund, A. N., Kopell, B. H., Golestani, N., Vornholt, E., Thompson, R. C., Liharska, L. E., Luo, Y., Cheng, E., Park, Y. J., Fennessy, B., et al. (2026) · Cell · doi:10.1016/j.cell.2025.10.014 · Cited by 6
Metadata
- Authors
- Liu, Y., El-Naggar, S., Darling, D. S., Higashi, Y., & Dean, D. C.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2008-02-01
- Volume
- 135
- Issue
- 3
- Pages
- 579-588
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2112575854
- Cited by
- 303
- References
- 7
- FWCI
- 12.67
- 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
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.
