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Review Open Access

Roles of β‑catenin protein in non‑small cell lung cancer (Review)

  • Authors:
    • Lina Peng
    • Ran Gao
    • Liping Han
    • Tian Fu
    • Cuixia Bian
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory and Critical Care Medicine, Jining First People's Hospital, Jining, Shandong 272000, P.R. China, Department of Respiratory Medicine, Jiaxiang People's Hospital, Jining, Shandong 272400, P.R. China
    Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 565
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    Published online on: October 1, 2025
       https://doi.org/10.3892/ol.2025.15311
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Abstract

Lung cancer remains the leading cause of cancer‑related death globally, with non‑small cell lung cancer (NSCLC) accounting for the majority of lung cancer cases. Therefore, understanding the mechanisms underlying NSCLC development is essential. Cancer cells can influence the tumor immune microenvironment, angiogenesis, apoptosis and epithelial‑mesenchymal transition (EMT) through various cell signaling pathways. Among these, the β‑catenin protein, encoded by the CTNNB1 gene, plays a pivotal role by precisely regulating the Wnt/β‑catenin signaling pathway, making it a critical factor in NSCLC pathogenesis. Although numerous studies have investigated β‑catenin, the present review integrates research published between 1997 and 2024 to provide a more recent comprehensive and systematic overview of the role of β‑catenin in the occurrence and development of NSCLC. Specifically, the present review examines the role of β‑catenin in the regulation of EMT and the tumor microenvironment, summarizes the regulatory mechanisms governing its nuclear translocation, explores its involvement in mediating resistance to EGFR tyrosine kinase inhibitors and evaluates its potential (alongside that of its coding gene) as a prognostic biomarker.
View Figures

Figure 1

Role of β-catenin in the canonical
Wnt signaling pathway. In the absence of the Wnt ligand, cytosolic
β-catenin binds to the destruction complex, leading to its
degradation. During this state, TCF/LEF transcription factors are
bound to co-repressor proteins and cannot initiate transcription.
When Wnt ligands bind to Frizzled receptors and LRP5/6, Dvl is
activated, which inactivates the destruction complex. This inhibits
β-catenin phosphorylation and degradation, allowing cytoplasmic
β-catenin to accumulate and translocate into the nucleus. There, it
can bind TCF/LEF transcription factors, thereby activating the
transcription of Wnt target genes and promoting cell proliferation
and epithelial-mesenchymal transition. TCF/LEF, T-cell
factor/lymphoid enhancer factor; LRP5/6, low-density lipoprotein
receptor-related protein 5/6; Dvl, Dishevelled; co-repressor pro,
co-repressor protein; EMT, epithelial-mesenchymal transition; CK1,
casein kinase-1; APC, adenomatous polyposis coli; βTrCP,
β-transducin repeat-containing protein; DKK1, Dickkopf-1.

Figure 2

Primary structure of β-catenin
protein. The β-catenin protein consists of three main domains: The
N-terminal, ARM repeat and C-terminal domains. The N-terminal
domain can bind to GSK-3β and CK1 for phosphorylation, a process
that regulates the degradation of β-catenin. The ARM repeat domain
binds to E-cadherin on the cell membrane, which enhances cell-cell
adhesion. The C-terminal domain binds to nuclear TCF/LEF
transcription factors, initiating the transcription of target
genes. ARM, A central armadillo; GSK-3β, glycogen synthase
kinase-3β; CK1, casein kinase-1; TCF/LEF, T-cell factor/lymphoid
enhancer factor.

Figure 3

Mechanisms by which β-catenin induces
resistance to EGFR-TKIs. β-catenin contributes to EGFR-TKI
resistance through several mechanisms including activation of EGFR
signaling, cooperation with bypass signals, regulation of nuclear
transcription and alteration of the tumor immune microenvironment.
ITGB1, β1 integrin; SRPK1, serine-arginine protein kinase 1; PAK2,
p21-activated kinase 2; CK1, casein kinase-1; APC, adenomatous
polyposis coli; βTrCP, β-transducin repeat-containing protein;
TCF/LEF, T-cell factor/lymphoid enhancer factor; CCND1, Cyclin D1
gene; EMT, epithelial-mesenchymal transition.
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Copy and paste a formatted citation
Spandidos Publications style
Peng L, Gao R, Han L, Fu T and Bian C: Roles of β‑catenin protein in non‑small cell lung cancer (Review). Oncol Lett 30: 565, 2025.
APA
Peng, L., Gao, R., Han, L., Fu, T., & Bian, C. (2025). Roles of β‑catenin protein in non‑small cell lung cancer (Review). Oncology Letters, 30, 565. https://doi.org/10.3892/ol.2025.15311
MLA
Peng, L., Gao, R., Han, L., Fu, T., Bian, C."Roles of β‑catenin protein in non‑small cell lung cancer (Review)". Oncology Letters 30.6 (2025): 565.
Chicago
Peng, L., Gao, R., Han, L., Fu, T., Bian, C."Roles of β‑catenin protein in non‑small cell lung cancer (Review)". Oncology Letters 30, no. 6 (2025): 565. https://doi.org/10.3892/ol.2025.15311
Copy and paste a formatted citation
x
Spandidos Publications style
Peng L, Gao R, Han L, Fu T and Bian C: Roles of β‑catenin protein in non‑small cell lung cancer (Review). Oncol Lett 30: 565, 2025.
APA
Peng, L., Gao, R., Han, L., Fu, T., & Bian, C. (2025). Roles of β‑catenin protein in non‑small cell lung cancer (Review). Oncology Letters, 30, 565. https://doi.org/10.3892/ol.2025.15311
MLA
Peng, L., Gao, R., Han, L., Fu, T., Bian, C."Roles of β‑catenin protein in non‑small cell lung cancer (Review)". Oncology Letters 30.6 (2025): 565.
Chicago
Peng, L., Gao, R., Han, L., Fu, T., Bian, C."Roles of β‑catenin protein in non‑small cell lung cancer (Review)". Oncology Letters 30, no. 6 (2025): 565. https://doi.org/10.3892/ol.2025.15311
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