Related Experiment Video

Updated: Feb 9, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

18.9K

TET1-Mediated Hypomethylation Activates Oncogenic Signaling in Triple-Negative Breast Cancer

Charly Ryan Good1, Shoghag Panjarian1, Andrew D Kelly1

  • 1Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.

Cancer Research
|June 13, 2018
PubMed

Insights

The TET1 DNA demethylase is overexpressed in triple-negative breast cancer (TNBC), promoting hypomethylation and activating oncogenic pathways. TET1 inhibition may offer a new therapeutic strategy for TNBC patients.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Genomics

Background:

  • DNA methylation patterns are altered in cancer, but the mechanisms controlling this dysregulation are not fully understood.
  • Triple-negative breast cancer (TNBC) is characterized by significant hypomethylation.
  • The role of TET1 DNA demethylase in TNBC pathogenesis and its prognostic implications require further investigation.

Purpose of the Study:

  • To investigate the role of TET1 DNA demethylase in triple-negative breast cancer (TNBC).
  • To explore the association between TET1 expression, DNA hypomethylation, and oncogenic pathway activation in TNBC.
  • To evaluate TET1 as a potential therapeutic target for TNBC.

Main Methods:

  • Bioinformatic analyses of TET1 expression in TNBC patient data and cancer cell line panels.
  • Correlation analysis of TET1 levels with CpG methylation status and patient survival.
  • CRISPR-mediated gene editing to assess the functional impact of TET1 deletion in TNBC cell lines.
  • Analysis of oncogenic and immune gene expression in response to TET1 modulation.

Main Results:

  • TET1 is overexpressed in approximately 40% of TNBC cases, correlating with widespread hypomethylation and poorer survival.
  • TET1 overexpression is linked to the activation of key oncogenic pathways, including PI3K, EGFR, and PDGF.
  • TET1 deletion in TNBC cells reduced PI3K pathway gene expression, increased immune response genes, and decreased proliferation.
  • TET1 expression correlated with sensitivity to PI3K-mTOR pathway inhibitors.

Conclusions:

  • TET1 acts as a potential oncogene in TNBC, driving aberrant hypomethylation and promoting cancer progression.
  • Targeting TET1 may represent a viable therapeutic strategy for a subset of TNBC patients.
  • Understanding the TET1-mediated epigenetic landscape is crucial for developing targeted therapies in breast cancer.

More Related Videos

Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System10:51

Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System

Published on: April 23, 2021

4.7K
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

20.7K

Related Concept Videos

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...
11.5K
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...
4.8K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.6K
Scalar and Vector Triple Products01:06

Scalar and Vector Triple Products

Two vectors can be multiplied using a scalar product or a vector product. The resultant of a scalar product is scalar, while with vector products, the resultant is a vector. These rules of the scalar or vector product between two vectors can be applied to multiple vectors to obtain meaningful combinations. The scalar triple product is the dot product of a vector with the cross product of two vectors.
The scalar triple product is the dot product of a vector with the cross product of two vectors....
4.5K
Receptor-mediated Endocytosis01:39

Receptor-mediated Endocytosis

Overview
111.1K
Paracrine Signaling01:21

Paracrine Signaling

Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
59.7K