Related Experiment Video

Updated: Jun 7, 2025

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

23.3K

ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer

Benedetto DiCiaccio1, Marco Seehawer1, Zheqi Li1

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Cell Reports
|November 21, 2024
PubMed

Insights

KDM5A amplification drives basal breast cancer growth. Inhibiting KDM5A suppresses tumors, with ZBTB7A deletion increasing sensitivity and RHO-GTPases conferring resistance, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • KDM5B is an oncogene in estrogen-receptor-positive breast cancer.
  • KDM5A is amplified and overexpressed in basal breast cancer subtypes.

Purpose of the Study:

  • Investigate KDM5A's role in basal breast cancer.
  • Identify mechanisms of sensitivity and resistance to KDM5 inhibition (KDM5i).

Main Methods:

  • CRISPR-Cas9 knockout screens.
  • Chromatin immunoprecipitation sequencing (ChIP-seq).
  • RNA sequencing (RNA-seq).

Main Results:

  • KDM5 inhibition suppresses KDM5-amplified basal breast cancer cell growth.
  • ZBTB7A deletion sensitizes cells to KDM5i; RHO-GTPase deletion confers resistance.
  • ZBTB7A is crucial for KDM5A chromatin binding and influences transcriptional responses.

Conclusions:

  • KDM5A is a therapeutic target in basal breast cancer.
  • ZBTB7A and RHO-GTPases are key mediators of KDM5i response.
  • High ZBTB7A expression correlates with poor chemotherapy response in triple-negative breast cancer.
Keywords:
CP: CancerCRISPR screenbreast cancerhistone demethylasemitochondrial signaling

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.5K

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
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...
3.7K
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
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
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...
3.0K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K