Related Experiment Video

Updated: Aug 7, 2025

Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets
07:08

Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets

Published on: February 2, 2024

876

BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma

Yuliang Feng, Liuyang Cai, Martin Pook

    Biorxiv : the Preprint Server for Biology
    |March 13, 2023
    PubMed

    Insights

    Bromodomain-containing protein 9 (BRD9) regulates pancreatic cancer stem cell (CSC) stemness. Inhibiting BRD9 blocks CSC self-renewal and invasiveness, offering a new therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC).

    Area of Science:

    • Oncology
    • Epigenetics
    • Molecular Biology

    Background:

    • Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, partly due to chemotherapy-resistant cancer stem-like cells (CSCs).
    • Identifying novel targets to overcome CSC-mediated resistance is crucial for improving PDAC treatment outcomes.

    Approach:

    • Conducted small molecule compound screening targeting 142 epigenetic enzymes to identify key regulators of pancreatic CSC stemness.
    • Investigated the role of bromodomain-containing protein 9 (BRD9), a component of the BAF complex, in orchestrating CSC stemness.
    • Utilized inhibition and genetic ablation of BRD9, alongside patient-derived xenografts (PDX) mouse models, to assess therapeutic potential.

    Key Points:

    • BRD9 inhibition and genetic ablation effectively block CSC self-renewal, cell cycle progression, and invasiveness.
    • BRD9 targeting enhances CSC sensitivity to gemcitabine chemotherapy.
    • Pharmacological inhibition of BRD9 significantly reduces PDAC tumorigenesis in vivo and eliminates CSCs in patient tumors.
    • BRD9 inhibition disrupts enhancer-promoter looping and stemness gene transcription in CSCs.

    Conclusions:

    • BRD9 is a critical chromatin regulator of pancreatic CSC stemness, cooperating with the TGFβ/Activin-SMAD2/3 pathway.
    • BRD9 represents a promising novel therapeutic target for PDAC, offering a strategy to modulate CSC stemness and overcome treatment resistance.

    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

    13.1K
    Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture08:16

    Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture

    Published on: February 11, 2019

    8.8K

    Related Concept Videos

    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...
    7.5K
    Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

    Role Of Notch Signalling In Intestinal Stem Cell Renewal

    Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
    Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
    2.2K
    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...
    4.6K
    Canonical Wnt Signaling Pathway02:54

    Canonical Wnt Signaling Pathway

    The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
    8.8K
    Cadherins in Tissue Organization01:19

    Cadherins in Tissue Organization

    The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
    Cell Sorting During Development
    Cell sorting plays an...
    3.1K
    Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

    Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

    Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
    2.3K