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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
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Activating transcription factor 3 is an antitumor gene synergizing with growth differentiation factor 15 to modulate

Syue-Ting Chen1, Kang-Shuo Chang2, Wei-Yin Lin3

  • 1Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.

Biomedical Journal
|June 28, 2024
PubMed
Abstract

Insights

Activating transcription factor 3 (ATF3) is an antitumor gene in bladder cancer, positively correlating with GDF15. Low ATF3/GDF15 levels indicate a poor prognosis, with ATF3 regulating tumor growth and invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The role of Activating Transcription Factor 3 (ATF3) in human bladder remains unknown.
  • This study investigates the expression, function, and regulation of ATF3 in human bladder cancer.

Purpose of the Study:

  • To explore the expression and function of ATF3 in human bladder cancer.
  • To determine the regulatory mechanisms of ATF3 in bladder cancer.
  • To evaluate ATF3/GDF15 as a prognostic marker for bladder cancer.

Main Methods:

  • Gene expression analysis (immunoblot, RT-qPCR, reporter assays).
  • In vitro and in vivo assays for cell proliferation, invasion, and tumorigenesis (Ki67, colony formation, Matrigel invasion, xenograft study).
  • Bioinformatic analysis of TCGA database for correlations between ATF3, GDF15, clinicopathologic features, and survival rates.

Main Results:

  • ATF3 acts as an antitumor gene, with its expression positively correlating with GDF15 in bladder cancer tissues.
  • Low ATF3/GDF15 ratio is an independent prognostic factor for progression-free survival in bladder cancer patients.
  • ATF3 overexpression suppressed proliferation and invasion, while ATF3 knockdown enhanced them; ATF3 regulates GDF15 via a feedback loop.

Conclusions:

  • ATF3 is a metformin-upregulated antitumor gene in bladder cancer.
  • The ATF3/GDF15 ratio serves as a potential negative prognostic marker for bladder cancer, supported by both bioinformatic and cell-based findings.
Keywords:
ATF3BladderEMTGDF15In silicoTumorigenesis

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