Related Experiment Video
Updated: Nov 26, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
ATF-3 expression inhibits melanoma growth by downregulating ERK and AKT pathways
Tingjian Zu1,2,3, Diana Wang3,4, Shuyun Xu3
1Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shangdong, China.
Abstract:
Activating transcription factor 3 (ATF-3), a cyclic AMP-dependent transcription factor, has been shown to play a regulatory role in melanoma, although its function during tumor progression remains unclear. Here, we demonstrate that ATF-3 exhibits tumor suppressive function in melanoma. Specifically, ATF-3 nuclear expression was significantly diminished with melanoma progression from nevi to primary to metastatic patient melanomas, correlating low expression with poor prognosis. Significantly low expression of ATF-3 was also found in cultured human metastatic melanoma cell lines. Importantly, overexpression of ATF-3 in metastatic melanoma cell lines significantly inhibited cell growth, migration, and invasion in vitro; as well as abrogated tumor growth in a human melanoma xenograft mouse model in vivo. RNA sequencing analysis revealed downregulation of ERK and AKT pathways and upregulation in apoptotic-related genes in ATF-3 overexpressed melanoma cell lines, which was further validated by Western-blot analysis. In summary, this study demonstrated that diminished ATF-3 expression is associated with melanoma virulence and thus provides a potential target for novel therapies and prognostic biomarker applications.
Insights
Activating transcription factor 3 (ATF-3) suppresses melanoma. Lower ATF-3 levels correlate with advanced melanoma, and restoring ATF-3 inhibits tumor growth and spread, indicating its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Activating transcription factor 3 (ATF-3) is a transcription factor involved in cellular stress responses.
- Its precise role in melanoma progression has been unclear.
- ATF-3 is known to be regulated by cyclic AMP.
Purpose of the Study:
- To investigate the function of ATF-3 in melanoma development and progression.
- To determine if ATF-3 expression levels correlate with melanoma severity.
- To evaluate ATF-3 as a potential therapeutic target or prognostic biomarker for melanoma.
Main Methods:
- Analysis of ATF-3 nuclear expression in melanoma patient samples at different stages (nevi, primary, metastatic).
- Overexpression of ATF-3 in metastatic melanoma cell lines and assessment of cellular functions (growth, migration, invasion) in vitro.
- Evaluation of tumor growth in a human melanoma xenograft mouse model in vivo.
- RNA sequencing and Western-blot analysis to identify molecular pathways affected by ATF-3.
Main Results:
- ATF-3 nuclear expression significantly decreased with melanoma progression.
- Low ATF-3 expression correlated with poor prognosis in melanoma patients.
- Overexpression of ATF-3 inhibited melanoma cell growth, migration, and invasion in vitro.
- ATF-3 overexpression abrogated tumor growth in vivo.
- RNA sequencing revealed ATF-3 modulates ERK and AKT pathways and affects apoptosis-related genes.
Conclusions:
- ATF-3 exhibits tumor suppressive functions in melanoma.
- Diminished ATF-3 expression is linked to melanoma virulence.
- ATF-3 represents a potential prognostic biomarker and therapeutic target for melanoma.
Related Concept Videos
MAPK Signaling Cascades
Mitogens and the Cell Cycle
PI3K/mTOR/AKT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The Tumor Microenvironment
The Intrinsic Apoptotic Pathway

