The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail
Open accessAbstract
The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic alpha subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL(-/-)) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIFalpha in CC-RCC (VHL(-/-)) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIFalpha degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin.
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
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
Self-citationOhh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T.-Y., Huang, L. E., Pavletich, N., Chau, V., & Kaelin, W. G. (2000) · Nature Cell Biology · doi:10.1038/35017054 · Cited by 1,577
Self-citationLaughner, E., Taghavi, P., Chiles, K., Mahon, P. C., & Semenza, G. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3995-4004.2001 · Cited by 1,256 · cited 1×
“The increased expression of HER2 receptor tyrosine kinase in breast cancer and the loss of p53 in various tumors enhance HIF-1-dependent transcription, often correlating with tumor aggressiveness (36, 55).”
BackgroundRegulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α
Ravi, R., Mookerjee, B., Bhujwalla, Z. M., Sutter, C. H., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., & Bedi, A. (2000) · Genes & Development · doi:10.1101/gad.14.1.34 · Cited by 967
Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHL
Staller, P., Sulitkova, J., Lisztwan, J., Moch, H., Oakeley, E. J., & Krek, W. (2003) · Nature · doi:10.1038/nature01874 · Cited by 870
Molecular basis of the VHL hereditary cancer syndrome
Kaelin, W. G. (2002) · Nature Reviews Cancer · doi:10.1038/nrc885 · Cited by 865
Loss of PTEN facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840
Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein
Kondo, K., Klco, J., Nakamura, E., Lechpammer, M., & Kaelin, W. G. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00043-0 · Cited by 761
Cited by
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
Direct regulation of TWIST by HIF-1α promotes metastasis
Yang, M.-H., Wu, M.-Z., Chiou, S.-H., Chen, P.-M., Chang, S.-Y., Liu, C.-J., Teng, S.-C., & Wu, K.-J. (2008) · Nature Cell Biology · doi:10.1038/ncb1691 · Cited by 1,345
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
The role of hypoxia-inducible factors in tumorigenesis
Rankin, E. B., & Giaccia, A. J. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.21 · Cited by 806
Involvement of Members of the Cadherin Superfamily in Cancer
Berx, G., & van Roy, F. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003129 · Cited by 709
Self-citation
Metadata
- Authors
- Evans, A. J., Russell, R. C., Roche, O., Burry, T. N., Fish, J. E., Chow, V. W. K., Kim, W. Y., Saravanan, A., Maynard, M. A., Gervais, M. L., Sufan, R. I., Roberts, A. M., Wilson, L. A., Betten, M., Vandewalle, C., Berx, G., Marsden, P. A., Irwin, M. S., Teh, B. T., Jewett, M. A. S., & Ohh, M.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-01-01
- Volume
- 27
- Issue
- 1
- Pages
- 157-169
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2104108149
- Cited by
- 248
- References
- 13
- FWCI
- 6.18
- 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: VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail. https://app.cochat.ai/papers/10.1128/mcb.00892-06
- The paper
- Evans, A. J., Russell, R. C., Roche, O., Burry, T. N., Fish, J. E., Chow, V. W. K., Kim, W. Y., Saravanan, A., Maynard, M. A., Gervais, M. L., Sufan, R. I., Roberts, A. M., Wilson, L. A., Betten, M., Vandewalle, C., Berx, G., Marsden, P. A., Irwin, M. S., Teh, B. T., . . . Ohh, M. (2007). VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.00892-06
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.
