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.

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.

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