Related Experiment Video

Updated: Jun 11, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

5.9K

NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction

Guozheng Li1, Xin Ma1, Shiyao Sui1

  • 1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150040, China.

Journal of Experimental & Clinical Cancer Research : CR
|October 4, 2024
PubMed
Abstract

Insights

The NAT10-ac4C-JunB-LDHA pathway drives tumor growth and immune suppression in triple-negative breast cancer (TNBC). Inhibiting this pathway with remodelin and CTLA-4 blockade offers a promising strategy for cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • N4-Acetylcytidine (ac4C) is a critical RNA modification involved in tumor progression.
  • The role of ac4C in mediating immunosuppression within triple-negative breast cancer (TNBC) remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms of ac4C-mediated immunosuppression in TNBC.
  • To investigate the therapeutic potential of targeting the NAT10-ac4C pathway in TNBC.

Main Methods:

  • Analysis of NAT10 expression and ac4C levels in TNBC tissues.
  • In vitro and in vivo studies on NAT10's effects on the immune microenvironment and tumor metabolism.
  • Exploration of combination therapy targeting NAT10 in TNBC models.

Main Results:

  • Loss of NAT10 inhibited TNBC growth and enhanced T cell activation.
  • NAT10 upregulates JunB via ac4C modification, which in turn increases LDHA and glycolysis.
  • NAT10 inhibition with remodelin increased CTLA-4 expression on T cells, enhancing anti-tumor immunity when combined with CTLA-4 blockade.

Conclusions:

  • The NAT10-ac4C-JunB-LDHA axis promotes glycolysis and immune suppression in TNBC.
  • Targeting this pathway presents a novel therapeutic strategy for improving cancer immunotherapy efficacy in TNBC.
Keywords:
CTLA-4GlycolysisImmunosuppressionN4-acetylcytidineNAT10/ac4C/JunB axisTriple negative breast cancer

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

6.4K
Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells06:07

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Published on: March 28, 2025

208

Related Concept Videos

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
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...
3.8K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
489
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
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...
857
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...
4.5K