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Homeobox Protein BarH-like 1 Promotes Gastric Cancer Progression by Activating Coiled-Coil Domain-Containing Protein
Yue Gu1, Gang Chen2, Xinwei Ning2
1Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, Yiyuan Street, Nangang District, 150001, Harbin, Heilongjiang, People's Republic of China. 840324@hrbmu.edu.cn.
Homeobox protein BarH-like 1 (BARX1) activates coiled-coil domain-containing protein 178 (CCDC178) transcription, promoting gastric cancer progression via the ERK pathway and macrophage polarization.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Coiled-coil domain-containing protein 178 (CCDC178) promotes metastasis in hepatocellular carcinoma.
- The role of CCDC178 in gastric cancer (GC) remains largely unknown.
- Understanding CCDC178's function in GC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of CCDC178 in gastric cancer (GC) progression.
- To elucidate the molecular mechanisms underlying CCDC178's function in GC.
- To identify potential therapeutic targets for GC treatment.
Main Methods:
- Bioinformatic analysis of GC datasets to identify prognostic genes.
- Loss- and gain-of-function assays to assess CCDC178, BARX1, and ERK pathway involvement.
- In vivo experiments to validate findings in a preclinical model.
Main Results:
- High CCDC178 expression correlates with poor GC prognosis and increased macrophage infiltration.
- CCDC178 activates the ERK pathway, enhancing GC cell proliferation, migration, and invasion.
- BARX1 transcriptionally upregulates CCDC178, promoting M2-like macrophage polarization.
Conclusions:
- BARX1-induced CCDC178 activation of the ERK pathway drives GC progression.
- This pathway supports tumor-associated macrophage (TAM) recruitment and M2-like polarization.
- Targeting the BARX1-CCDC178-ERK axis offers a potential therapeutic strategy for GC.
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