Related Experiment Video

Updated: May 9, 2025

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
07:44

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports

Published on: November 28, 2019

7.4K

Epigenetic silencing of DNA sensing pathway by FOXM1 blocks stress ligand-dependent antitumor immunity and immune

Santosh Timilsina1, Jian Yu Huang1, Nourhan Abdelfattah2

  • 1Greehey Children's Cancer Research Institute, San Antonio, TX, USA.

Nature Communications
|April 28, 2025
PubMed

Insights

Transcription factor FOXM1 suppresses anti-tumor immunity by epigenetically silencing STING, leading to poor survival and immunotherapy response in cancer patients. This reveals a key mechanism in shaping the tumor immune microenvironment.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor microenvironment and cancer cell interactions critically impact cancer progression.
  • Transcription factors play a role in modulating the tumor immune landscape.

Purpose of the Study:

  • To investigate the role of transcription factor FOXM1 in shaping the tumor immune microenvironment.
  • To elucidate the molecular mechanisms by which FOXM1 influences anti-tumor immunity.

Main Methods:

  • Single-cell sequencing to analyze tumor-intrinsic gene expression.
  • Epigenetic analysis to understand gene silencing mechanisms.
  • Correlation of gene expression with patient survival and immunotherapy response.

Main Results:

  • Tumor-intrinsic FOXM1 suppresses immune responses by inhibiting stress ligand ULBP1 expression on cancer cells.
  • FOXM1 epigenetically silences STING via a DNMT1-UHRF1 complex, blocking CHOP-mediated ULBP1 activation.
  • High FOXM1/DNMT1 and low STING/ULBP1 correlate with worse patient survival and immunotherapy resistance.

Conclusions:

  • FOXM1 epigenetically reprograms the tumor immune microenvironment towards immune suppression.
  • Targeting the FOXM1-STING-ULBP1 axis may enhance cancer immunotherapy efficacy.
  • Understanding this mechanism offers new strategies for cancer treatment.

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.7K
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

11.2K

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...
4.3K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
2.9K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.6K
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...
3.6K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.1K
Psychoneuroimmunology: Diabetes and Cancer01:19

Psychoneuroimmunology: Diabetes and Cancer

Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
16