E3 ubiquitin ligase MAGI3-mediated TAZ ubiquitination suppresses the non-small cell lung cancer occurrence and development by targeting the Wnt pathway
- 1Department of Allergy, Qingdao Integrated Chinese and Western Medicine Hospital, Qingdao, Shandong 266000, P.R. China
- 2Department of Rehabilitation Medicine, The Third People's Hospital of Qingdao, Qingdao, Shandong 266041, P.R. China
Abstract
Membrane associated guanylate kinase WW and PDZ domain containing 3 (MAGI3) functions as a tumor suppressor in lung cancer, but its role and mechanism in non-small cell lung cancer (NSCLC) progression remain unclear. MAGI3 expression was detected in NSCLC tissues (immunohistochemistry) and cell lines (western blotting). Tet-on inducible MAGI3 overexpression was used to assess effects on NSCLC cells via Cell Counting Kit-8, Transwell, colony/sphere formation, β-Galactosidase staining and flow cytometry. Ubiquitination/half-life assays analyzed MAGI3-TAZ (transcriptional co-activator with PDZ-binding motif) interaction. In situ and xenograft tumor models evaluated tumor growth and metastasis. The Cancer Genome Atlas data, clinical samples, and cell lines showed downregulated MAGI3 in NSCLC, correlating with poor prognosis. MAGI3 overexpression reduced cell viability, clonogenicity, sphere formation, migration and invasion; induced G1 phase arrest (reduced CyclinD1) and cellular senescence. MAGI3 specifically promoted TAZ ubiquitination via PDZ domain-mediated interaction, which subsequently blocked β-catenin nuclear translocation, dampened Wnt signaling components (DVL2/phosphorylated GSK3β), and reduced TCF/LEF transcriptional output. Reconstitution of TAZ reversed MAGI3-mediated inhibition of Wnt pathway markers (cMYC, c-JUN, WISP1 and PPARD). In vivo, MAGI3 overexpression suppressed tumor growth and lung metastasis, while MAGI3 silencing increased metastatic nodules. The present study identified that MAGI3, as a suppressor in NSCLC progression, repressed the Wnt pathway-including TAZ degradation, impaired β-catenin nuclear translocation, and diminished TCF/LEF transcription-thereby restraining tumorigenesis and metastasis of NSCLC.
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BibTeX
@article{liang2026ubiquitin,
title = {{E3 ubiquitin ligase MAGI3-mediated TAZ ubiquitination suppresses the non-small cell lung cancer occurrence and development by targeting the Wnt pathway}},
author = {Ye Liang and Jie Zhuang},
journal = {International Journal of Oncology},
year = {2026},
month = sep,
doi = {10.3892/ijo.2026.5939},
url = {https://doi.org/10.3892/ijo.2026.5939},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - E3 ubiquitin ligase MAGI3-mediated TAZ ubiquitination suppresses the non-small cell lung cancer occurrence and development by targeting the Wnt pathway
AU - Ye Liang
AU - Jie Zhuang
PY - 2026
DA - 2026/09/16
JO - International Journal of Oncology
DO - 10.3892/ijo.2026.5939
UR - https://doi.org/10.3892/ijo.2026.5939
AB - Membrane associated guanylate kinase WW and PDZ domain containing 3 (MAGI3) functions as a tumor suppressor in lung cancer, but its role and mechanism in non-small cell lung cancer (NSCLC) progression remain unclear. MAGI3 expression was detected in NSCLC tissues (immunohistochemistry) and cell lines (western blotting). Tet-on inducible MAGI3 overexpression was used to assess effects on NSCLC cells via Cell Counting Kit-8, Transwell, colony/sphere formation, β-Galactosidase staining and flow cytometry. Ubiquitination/half-life assays analyzed MAGI3-TAZ (transcriptional co-activator with PDZ-binding motif) interaction. In situ and xenograft tumor models evaluated tumor growth and metastasis. The Cancer Genome Atlas data, clinical samples, and cell lines showed downregulated MAGI3 in NSCLC, correlating with poor prognosis. MAGI3 overexpression reduced cell viability, clonogenicity, sphere formation, migration and invasion; induced G1 phase arrest (reduced CyclinD1) and cellular senescence. MAGI3 specifically promoted TAZ ubiquitination via PDZ domain-mediated interaction, which subsequently blocked β-catenin nuclear translocation, dampened Wnt signaling components (DVL2/phosphorylated GSK3β), and reduced TCF/LEF transcriptional output. Reconstitution of TAZ reversed MAGI3-mediated inhibition of Wnt pathway markers (cMYC, c-JUN, WISP1 and PPARD). In vivo, MAGI3 overexpression suppressed tumor growth and lung metastasis, while MAGI3 silencing increased metastatic nodules. The present study identified that MAGI3, as a suppressor in NSCLC progression, repressed the Wnt pathway-including TAZ degradation, impaired β-catenin nuclear translocation, and diminished TCF/LEF transcription-thereby restraining tumorigenesis and metastasis of NSCLC.
SN - 1019-6439
SN - 1791-2423
ER -