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Updated: Nov 5, 2025

Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
Published on: June 13, 2019
NT5DC2 promotes leiomyosarcoma tumour cell growth via stabilizing unpalmitoylated TEAD4 and generating a positive
Bowen Hu1, Shijie Zhou2, Xuefeng Hu3
1Department of Orthopedics, Orthopedics Research Institute, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncoprotein, the regulatory effects of which have not been well characterized. This study aimed to investigate the expression profile and functional regulation of NT5DC2 and its potential interplay with TEAD4 in leiomyosarcoma (LMS). Bioinformatic analysis was conducted using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) program. LMS cell lines SK-LMS-1 and SK-UT-1 were used for both in vitro and in vivo analysis. Results showed that NT5DC2 is aberrantly upregulated in LMS. Its overexpression was associated with unfavourable survival. Deletion of NT5DC2 significantly reduced the expression of cyclin B1, cyclin A2, cyclin E1 and CDK1 and increased G1 phase arrest in LMS cell lines, and suppressed their proliferation both in vitro and in vivo. NT5DC2 interacted with unpalmitoylated TEAD4, and this association reduced TEAD4 degradation via the ubiquitin-proteasome pathway. TRIM27 is a novel E3 ubiquitin ligase that induces K27/48-linked ubiquitination of unpalmitoylated TEAD4 at Lys278. TEAD4 inhibition significantly suppressed LMS cell growth both in vitro and in vivo. Dual-luciferase assay demonstrated that TEAD4 could bind to the NT5DC2 promoter and activate its transcription. Based on these findings, we infer that the NT5DC2-TEAD4 positive feedback loop plays an important role in LMS development and might serve as a potential therapeutic target.
Insights
5'-Nucleotidase Domain Containing 2 (NT5DC2) is upregulated in leiomyosarcoma (LMS), promoting cancer growth by stabilizing TEAD4. Inhibiting this NT5DC2-TEAD4 loop offers a potential therapeutic strategy for LMS.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- 5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncoprotein with poorly understood regulatory functions.
- Leiomyosarcoma (LMS) is a challenging cancer where novel therapeutic targets are needed.
Purpose of the Study:
- To investigate the expression, regulation, and function of NT5DC2 in LMS.
- To explore the interplay between NT5DC2 and TEAD4 in LMS pathogenesis.
Main Methods:
- Bioinformatic analysis using TCGA and GTEx data.
- In vitro and in vivo studies using LMS cell lines (SK-LMS-1, SK-UT-1).
- Analysis of protein interactions, ubiquitination, cell cycle, proliferation, and gene transcription.
Main Results:
- NT5DC2 is aberrantly upregulated in LMS and associated with poor survival.
- NT5DC2 deletion suppressed LMS cell proliferation by inducing G1 phase arrest and reducing cell cycle gene expression.
- NT5DC2 stabilized unpalmitoylated TEAD4 by inhibiting its proteasomal degradation, while TEAD4 activated NT5DC2 transcription, forming a positive feedback loop.
Conclusions:
- The NT5DC2-TEAD4 positive feedback loop is crucial for LMS development.
- Targeting the NT5DC2-TEAD4 axis presents a potential therapeutic strategy for leiomyosarcoma.
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