Related Experiment Video

Updated: Jul 10, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

A potential dichotomous role of ATF3, an adaptive-response gene, in cancer development

X Yin1, J W Dewille, T Hai

  • 1The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH, USA.

Oncogene
|October 24, 2007
PubMed

Insights

Activating transcription factor 3 (ATF3) plays a dual role in cancer. While it promotes apoptosis in normal cells, ATF3 enhances aggressive cancer cell motility and metastasis, suggesting an oncogenic function in tumors.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Activating transcription factor 3 (ATF3) is a transcription factor belonging to the ATF/cyclic AMP response element-binding family.
  • The role of ATF3 in cancer development is not fully understood, with potential for diverse functions.

Purpose of the Study:

  • To investigate the dichotomous role of ATF3 in cancer development.
  • To determine the specific molecular mechanisms by which ATF3 influences cancer cell behavior and gene expression.

Main Methods:

  • Gain- and loss-of-function experiments in mammary epithelial cells (MCF10A and MCF10CA1a).
  • Gene expression array analyses.
  • Chromatin immunoprecipitation (ChIP) assays to assess promoter binding.
  • Conditioned medium experiments to evaluate paracrine/autocrine effects.
  • Analysis of ATF3 gene copy number and protein levels in breast tumors.

Main Results:

  • ATF3 enhances apoptosis in untransformed MCF10A cells.
  • ATF3 protects aggressive MCF10CA1a cells and promotes their motility.
  • ATF3 upregulates tumor necrosis factor pathway genes in MCF10A cells.
  • ATF3 upregulates metastasis-implicated genes (TWIST1, FN-1, Slug, etc.) in MCF10CA1a cells.
  • ATF3 directly regulates the transcription of TWIST1, FN-1, Snail, and Slug genes.
  • ATF3 exhibits paracrine/autocrine effects.
  • Elevated ATF3 gene copy number (>2 in ~80%) and protein levels (~50%) in breast tumors.

Conclusions:

  • ATF3 exhibits a dichotomous role in cancer, promoting apoptosis in normal cells but enhancing aggressive cancer cell phenotypes.
  • ATF3's oncogenic roles in metastasis and cell motility are supported by its regulation of key genes and its prevalence in breast tumors.
  • The findings suggest that ATF3 expression is advantageous for malignant cancer cells.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...