The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling
Open accessAbstract
Epigenetic dysregulation has emerged as a major contributor to tumorigenesis. Histone methylation is a well-established mechanism of epigenetic regulation that is dynamically modulated by histone methyltransferases and demethylases. The pathogenic role of histone methylation modifiers in non-small cell lung cancer (NSCLC), which is the leading cause of cancer deaths worldwide, remains largely unknown. Here, we found that the histone H3 lysine 36 (H3K36) demethylase KDM2A (also called FBXL11 and JHDM1A) is frequently overexpressed in NSCLC tumors and cell lines. KDM2A and its catalytic activity were required for in vitro proliferation and invasion of KDM2A-overexpressing NSCLC cells. KDM2A overexpression in NSCLC cells with low KDM2A levels increased cell proliferation and invasiveness. KDM2A knockdown abrogated tumor growth and invasive abilities of NSCLC cells in mouse xenograft models. We identified dual-specificity phosphatase 3 (DUSP3) as a key KDM2A target gene and found that DUSP3 dephosphorylates ERK1/2 in NSCLC cells. KDM2A activated ERK1/2 through epigenetic repression of DUSP3 expression via demethylation of dimethylated H3K36 at the DUSP3 locus. High KDM2A levels correlated with poor prognosis in NSCLC patients. These findings uncover an unexpected role for a histone methylation modifier in activating ERK1/2 in lung tumorigenesis and metastasis, suggesting that KDM2A may be a promising therapeutic target in NSCLC.
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
High-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129
Cancer epigenetics: from mechanism to therapy
Dawson, M. A., & Kouzarides, T. (2012) · Cell · doi:10.1016/j.cell.2012.06.013 · Cited by 3,203
Epidermal growth factor receptor mutations in lung cancer
Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2088 · Cited by 3,170
Characterizing the cancer genome in lung adenocarcinoma
Weir, B. A., Woo, M. S., Getz, G., Perner, S., Ding, L., Beroukhim, R., Lin, W. M., Province, M. A., Kraja, A., Johnson, L. A., et al. (2007) · Nature · doi:10.1038/nature06358 · Cited by 1,105
Targeting dual-specificity phosphatases: Manipulating MAP kinase signalling and immune responses
Jeffrey, K. L., Camps, M., Rommel, C., & Mackay, C. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2289 · Cited by 533
Wang, T., Chen, K., Zeng, X., Yang, J., Wu, Y., Shi, X., Qin, B., Zeng, L., Esteban, M. A., Pan, G., et al. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.10.005 · Cited by 458
Cited by
Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials
Cheng, Y., He, C., Wang, M., Ma, X., Mo, F., Yang, S., Han, J., & Wei, X. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0095-0 · Cited by 1,097
Lung cancer epigenetics: From knowledge to applications
Duruisseaux, M., & Esteller, M. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.09.005 · Cited by 283
KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer
Alam, H., Tang, M., Maitituoheti, M., Dhar, S. S., Kumar, M., Han, C. Y., Ambati, C. R., Amin, S. B., Gu, B., Chen, T.-Y., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.005 · Cited by 243
Self-citationMolecular pathways and therapeutic targets in lung cancer
Shtivelman, E., Hensing, T., Simon, G. R., Dennis, P. A., Otterson, G. A., Bueno, R., & Salgia, R. (2014) · Oncotarget · doi:10.18632/oncotarget.1891 · Cited by 220
“High KDM2A levels are associated with low DUSP3, high phospho-ERK levels, and poor prognosis [192].”
BackgroundTumor hypoxia: From basic knowledge to therapeutic implications
Liao, C., Liu, X., Zhang, C., & Zhang, Q. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.12.011 · Cited by 223
Metadata
- Authors
- Wagner, K. W., Alam, H., Dhar, S. S., Giri, U., Li, N., Wei, Y., Giri, D., Cascone, T., Kim, J.-H., Ye, Y., Multani, A. S., Chan, C.-H., Erez, B., Saigal, B., Chung, J., Lin, H.-K., Wu, X., Hung, M.-C., Heymach, J. V., & Lee, M. G.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-11-08
- Volume
- 123
- Issue
- 12
- Pages
- 5231-5246
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2082854050
- Cited by
- 193
- References
- 7
- FWCI
- 6.86
- 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: KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling. https://app.cochat.ai/papers/10.1172/jci68642
- The paper
- Wagner, K. W., Alam, H., Dhar, S. S., Giri, U., Li, N., Wei, Y., Giri, D., Cascone, T., Kim, J.-H., Ye, Y., Multani, A. S., Chan, C.-H., Erez, B., Saigal, B., Chung, J., Lin, H.-K., Wu, X., Hung, M.-C., Heymach, J. V., & Lee, M. G. (2013). KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling. Journal of Clinical Investigation. https://doi.org/10.1172/jci68642
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.
