Cited by 274Wnt/β-catenin signaling in development and cancerSignaling Pathways in DiseaseProtein Kinase Regulation and GTPase Signaling

EGF-Induced ERK Activation Promotes CK2-Mediated Disassociation of α-Catenin from β-Catenin and Transactivation of β-Catenin

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Ji, Haitao, Wang, Ji, Nika, Heinz, Hawke, David, Keezer, Susan, Ge, Qingyuan, Fang, Bingliang, Fang, Xuexun +4 more·2009·Molecular Cell

Abstract

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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Crossref · 10.1016/j.molcel.2009.09.034

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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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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
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2009-11
Volume
36
Issue
4
Pages
547-559
ISSN
1097-2765 (ISSN-L)
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
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

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