Related Experiment Video

Updated: Apr 25, 2026

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

2.7K

Cell crowding induces interferon regulatory factor 9, which confers resistance to chemotherapeutic drugs

Iryna Kolosenko1, Mårten Fryknäs, Sofi Forsberg

  • 1Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, 17176, Stockholm, Sweden.

International Journal of Cancer
|August 27, 2014
PubMed

Insights

Cell crowding in solid tumors upregulates interferon regulatory factor-9 (IRF9), driving drug resistance by increasing interferon-stimulated genes (ISGs). This reveals a new mechanism for overcoming chemotherapy resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Multicellular drug resistance in solid tumors reduces chemotherapy efficacy.
  • The precise mechanisms underlying this phenomenon remain incompletely understood.

Purpose of the Study:

  • To investigate the biological mechanisms driving drug resistance in solid tumors.
  • To identify key molecular players involved in multicellular drug resistance.

Main Methods:

  • Culturing colon carcinoma cells as 3D microtissues (spheroids) to mimic solid tumors.
  • Analyzing gene expression changes, specifically interferon-stimulated genes (ISGs).
  • Utilizing gene knock-down studies and examining the role of Interferon Regulatory Factor-9 (IRF9).

Main Results:

  • 3D spheroids exhibited significantly increased expression of a subset of ISGs.
  • Cell crowding induced Interferon Regulatory Factor-9 (IRF9) expression, which, with STAT2 and independent of interferons (IFNs), upregulated ISGs.
  • Elevated IRF9 expression alone conferred drug resistance in monolayer cells.

Conclusions:

  • A novel mechanism for ISG regulation has been identified, contributing to drug resistance in solid tumors.
  • IRF9 is a key mediator of ISG upregulation and subsequent chemoresistance in a cell-crowding context.
Keywords:
IRF9STAT transcription factorschemoresistanceinterferon-stimulated genesmulticellular spheroids

More Related Videos

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice07:36

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

6.8K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

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

Published on: January 7, 2019

7.7K

Related Concept Videos

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...
2.6K
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
55
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.4K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
7.0K
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,...
5.7K
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...
5.2K