EGF-Induced ERK Activation Promotes CK2-Mediated Disassociation of α-Catenin from β-Catenin and Transactivation of β-Catenin
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Increased transcriptional activity of beta-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation remains unclear. We demonstrate here that EGFR activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via CK2alpha-dependent phosphorylation of alpha-catenin at S641. ERK2, which is activated by EGFR signaling, directly binds to CK2alpha via the ERK2 docking groove and phosphorylates CK2alpha primarily at T360/S362, subsequently enhancing CK2alpha activity toward alpha-catenin phosphorylation. In addition, levels of alpha-catenin S641 phosphorylation correlate with levels of ERK1/2 activity in human glioblastoma specimens and with grades of glioma malignancy. This EGFR-ERK-CK2-mediated phosphorylation of alpha-catenin promotes beta-catenin transactivation and tumor cell invasion. These findings highlight the importance of the crosstalk between EGFR and Wnt pathways in tumor development.
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The crosstalk between the ERK and Wnt/β-catenin pathways has not been previously described in ccRCC, particularly under the regulation of PPP1R18.
“The crosstalk between the ERK and Wnt/β-catenin pathways, while reported in other cancers, has not been previously described in ccRCC, particularly under the regulation of PPP1R18”
From PPP1R18-mediated activation of Wnt/β-catenin and EMT is dependent on ERK signaling in clear cell renal cell carcinoma (2026) · cites this paper as [44]
The Abstract and Discussion describe ERK-mediated activation of β-catenin signaling in tumor cells, with evidence from human glioblastoma specimens. They support the statement that this interplay has been reported in other cancers, but do not address ccRCC or PPP1R18 and cannot establish the claimed absence of prior reports in that setting. (LLM, conf=0.85)
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Self-citation
- Authors
- Ji, H., Wang, J., Nika, H., Hawke, D., Keezer, S., Ge, Q., Fang, B., Fang, X., Fang, D., Litchfield, D. W., Aldape, K., & Lu, Z.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Cell Signaling Technology (United States) (US)
- Jilin University (CN)
- Western University (CA)
- Corresponding author
- Lu, Zhimin
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 36
- Issue
- 4
- Pages
- 547-559
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2784926
- OpenAlex
- W2011463708
- Cited by
- 270
- References
- 80
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 11 · 2023: 20 · 2022: 10 · 2021: 14 · 2020: 11 · 2019: 14 · 2018: 13 · 2017: 15 · 2016: 24 · 2015: 25 · 2014: 14 · 2013: 24 · 2012: 19
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- National Cancer Institute (R01CA109035)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- EGFR signaling, ERK2, CK2α, alpha-catenin, β-catenin, protein phosphorylation, tumor invasion, glioblastoma, cell adhesion complexes
- MeSH terms
- Amino Acid Sequence, Binding Sites, Enzyme Activation, Epidermal Growth Factor, Glioblastoma, Humans, Molecular Sequence Data, Neoplasm Invasiveness, Phosphorylation, Phosphoserine, Protein Binding, Transcriptional Activation, Casein Kinase II, Extracellular Signal-Regulated MAP Kinases, beta Catenin, alpha Catenin, ErbB Receptors
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 ›
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