Related Experiment Video
Updated: Jan 6, 2026
08:49
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
16.5K
COMMD4 Drives Skin Cutaneous Melanoma Progression by Targeting PI3K-p85 to Activate PI3K-AKT
Xiaoqiang Liu1,2, Luojia Liu2, Qiaoling Wang2
1Department of Plastic Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
Annals of the New York Academy of Sciences
|November 24, 2025
Summary
COMMD4 is a key driver in skin cutaneous melanoma (SKCM) progression, promoting cell growth and spread. Targeting the COMMD4-PI3K-AKT pathway with triamterene offers a new therapeutic strategy for SKCM.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Skin cutaneous melanoma (SKCM) is an aggressive cancer with poorly understood molecular mechanisms.
- The COMMD protein family's role in SKCM oncogenesis is largely undefined.
- Identifying novel prognostic biomarkers and therapeutic targets is crucial for improving SKCM outcomes.
Purpose of the Study:
- To investigate the functional relevance of COMMD4 in SKCM.
- To elucidate the molecular mechanisms by which COMMD4 regulates SKCM progression.
- To identify potential therapeutic agents targeting the COMMD4 pathway in SKCM.
Main Methods:
- Gene knockout (COMMD4-KO) in SKCM cells to assess proliferation, migration, and invasion in vitro.
- Xenograft tumor growth assays in vivo to evaluate COMMD4's role in tumor suppression.
- Analysis of cell cycle regulation (G2/M phase arrest) and epithelial-mesenchymal transition (EMT) markers.
- Investigation of the PI3K-AKT signaling pathway activation and its interaction with COMMD4.
- Integrative Connectivity Map analysis and functional validation to identify pharmacological inhibitors.
Main Results:
- COMMD4 acts as a prognostic biomarker positively correlated with adverse SKCM outcomes.
- COMMD4 knockout impaired SKCM cell proliferation, migration, invasion, and suppressed tumor growth.
- COMMD4 disruption led to G2/M phase arrest and impeded EMT by affecting E/N cadherin.
- COMMD4 activates PI3K-AKT signaling, driving G2/M transition and EMT; PI3K-AKT reactivation rescued oncogenic phenotypes.
- Triamterene was identified as a pharmacological inhibitor targeting the COMMD4-PI3K-AKT axis, suppressing SKCM progression.
Conclusions:
- The COMMD4-PI3K-AKT axis is a critical regulator of SKCM progression.
- COMMD4 plays a significant role in driving SKCM cell proliferation, migration, invasion, and EMT.
- Triamterene is a promising repurposed therapeutic agent for SKCM by targeting the COMMD4-PI3K-AKT pathway.
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