Related Experiment Video

Updated: Sep 9, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.4K

DFFB suppresses interferon to enable cancer persister cell regrowth

August F Williams1, David A G Gervasio1, Claire E Turkal1

  • 1Department of Dermatology, School of Medicine, University of California San Diego.

Biorxiv : the Preprint Server for Biology
|September 2, 2025
PubMed

Insights

Cancer cells surviving targeted therapy are growth-arrested by interferon signaling. These cells paradoxically use apoptosis to suppress this signaling, enabling regrowth and promoting drug resistance.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • Targeted cancer therapies can induce deep responses but often lead to acquired drug resistance.
  • Tumor evolution and multiple resistance mechanisms complicate treatment of resistant cancers.
  • Understanding and preventing adaptive resistance mechanisms is crucial for effective cancer therapy.

Purpose of the Study:

  • Investigate the mechanisms by which residual cancer persister cells survive oncogene-targeted therapy.
  • Identify the adaptive processes that initiate drug resistance in cancer persister cells.
  • Determine how persister cells escape growth arrest to promote tumor regrowth.

Main Methods:

  • Analysis of residual cancer persister cells surviving oncogene-targeted therapy.
  • Investigated the role of Type I interferon (IFN) signaling in growth arrest.
  • Examined the involvement of apoptotic machinery, DNA Fragmentation Factor B (DFFB/CAD), and Activating Transcription Factor 3 (ATF3) in persister cell adaptation.

Main Results:

  • Drug stress induces intrinsic Type I interferon (IFN) signaling, causing growth arrest in cancer persister cells.
  • Persister cells suppress interferon-stimulated genes (ISGs) by leveraging apoptotic pathways.
  • Sublethal activation of DFFB/CAD by caspases leads to ATF3-mediated suppression of ISGs, facilitating persister cell regrowth.
  • DFFB or ATF3 deficient persister cells show high ISG expression and fail to regrow.

Conclusions:

  • Sublethal apoptotic stress paradoxically promotes the regrowth of residual cancer cells that survive drug treatment.
  • The DFFB-ATF3 axis is essential for cancer persister cells to overcome IFN-induced growth arrest and acquire drug resistance.
  • Targeting this apoptotic-driven adaptive mechanism could offer novel strategies to overcome acquired resistance in cancer therapy.

More Related Videos

A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers10:49

A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers

Published on: September 26, 2019

5.7K
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice07:17

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice

Published on: June 22, 2016

10.0K

Related Concept Videos

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...
4.6K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.3K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K