The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
High Frequency of PIK3R1 and PIK3R2 Mutations in Endometrial Cancer Elucidates a Novel Mechanism for Regulation of PTEN Protein Stability
Open accessAbstract
We demonstrate that phosphatidylinositol 3-kinase (PI3K) pathway aberrations occur in >80% of endometrioid endometrial cancers, with coordinate mutations of multiple PI3K pathway members being more common than predicted by chance. PIK3R1 (p85α) mutations occur at a higher rate in endometrial cancer than in any other tumor lineage, and PIK3R2 (p85β), not previously demonstrated to be a cancer gene, is also frequently mutated. The dominant activation event in the PI3K pathway appears to be PTEN protein loss. However, in tumors with retained PTEN protein, PI3K pathway mutations phenocopy PTEN loss, resulting in pathway activation. KRAS mutations are common in endometrioid tumors activating independent events from PI3K pathway aberrations. Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85α dimers bind and stabilize PTEN. Taken together, the PI3K pathway represents a critical driver of endometrial cancer pathogenesis and a novel therapeutic target. Significance: Our data indicate that the PI3K pathway is targeted in the vast majority of endometrioid endometrial cancers leading to PI3K pathway activation. Frequent oncogenic mutations in PIK3R1 and PIK3R2 provide evidence for their role in endometrial cancer pathophysiology with patient-specific mutations revealing a novel mechanism by which p85α regulates the PI3K pathway through stabilizing PTEN. Cancer Discovery; 1(2); 170–85. ©2011 AACR. Read the Commentary on this article by Herrero-Gonzalez and Di Cristofano, p. 106 This article is highlighted in the In This Issue feature, p. 91
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
1 retracted
Ueki, K., Fruman, D. A., Yballe, C. M., Fasshauer, M., Klein, J., Asano, T., Cantley, L. C., & Kahn, C. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305602200 · Cited by 208
Self-citationRetractedComprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
High Frequency of Mutations of the PIK3CA Gene in Human Cancers
Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,437
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278
Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery
Hennessy, B. T., Smith, D. L., Ram, P. T., Lu, Y., & Mills, G. B. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1902 · Cited by 2,185
Self-citationEngelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330
Self-citationThe PI3K Pathway As Drug Target in Human Cancer
Courtney, K. D., Corcoran, R. B., & Engelman, J. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.3641 · Cited by 1,237
An integrative genomic and proteomic analysis of pik3ca, pten, and akt mutations in breast cancer.
Stemke-Hale, K., Gonzalez-Angulo, A. M., Lluch, A., Neve, R. M., Kuo, W.-L., Davies, M., Carey, M., Hu, Z., Guan, Y., Sahin, A., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6854 · Cited by 1,054
Self-citationTenets of PTEN Tumor Suppression
Salmena, L., Carracedo, A., & Pandolfi, P. P. (2008) · Cell · doi:10.1016/j.cell.2008.04.013 · Cited by 1,034
Phosphorylation of the PTEN Tail Regulates Protein Stability and Function
Vazquez, F., Ramaswamy, S., Nakamura, N., & Sellers, W. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.14.5010-5018.2000 · Cited by 774
Cited by
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
PI3K/AKT signaling pathway and cancer: An updated review
Martini, M., De Santis, M. C., Braccini, L., Gulluni, F., & Hirsch, E. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.912836 · Cited by 1,020
Compromised MAPK signaling in human diseases: an update
Kim, E. K., & Choi, E.-J. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1472-2 · Cited by 1,020
Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy
Shi, H., Hugo, W., Kong, X., Hong, A., Koya, R. C., Moriceau, G., Chodon, T., Guo, R., Johnson, D. B., Dahlman, K. B., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0642 · Cited by 982
Metadata
- Authors
- Cheung, L. W. T., Hennessy, B. T., Li, J., Yu, S., Myers, A. P., Djordjevic, B., Lu, Y., Stemke-Hale, K., Dyer, M. D., Zhang, F., Ju, Z., Cantley, L. C., Scherer, S. E., Liang, H., Lu, K. H., Broaddus, R. R., & Mills, G. B.
- Venue
- Cancer Discovery
- Published
- 2011-07-01
- Volume
- 1
- Issue
- 2
- Pages
- 170-185
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2167264978
- Cited by
- 470
- References
- 47
- FWCI
- 13.28
- Type
- journal article
- Language
- en
- Open access
- bronze
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: High Frequency of PIK3R1 and PIK3R2 Mutations in Endometrial Cancer Elucidates a Novel Mechanism for Regulation of PTEN Protein Stability. https://app.cochat.ai/papers/10.1158/2159-8290.cd-11-0039
- The paper
- Cheung, L. W. T., Hennessy, B. T., Li, J., Yu, S., Myers, A. P., Djordjevic, B., Lu, Y., Stemke-Hale, K., Dyer, M. D., Zhang, F., Ju, Z., Cantley, L. C., Scherer, S. E., Liang, H., Lu, K. H., Broaddus, R. R., & Mills, G. B. (2011). High Frequency of PIK3R1 and PIK3R2 Mutations in Endometrial Cancer Elucidates a Novel Mechanism for Regulation of PTEN Protein Stability. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-11-0039
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.
