Related Experiment Video

Updated: Sep 5, 2025

Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
08:01

Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal

Published on: May 30, 2012

10.6K

PFKFB3 works on the FAK-STAT3-SOX2 axis to regulate the stemness in MPM

Sayantani Sarkar Bhattacharya1,2,3, Prabhu Thirusangu1, Ling Jin1

  • 1Department of Experimental Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.

British Journal of Cancer
|July 6, 2022
PubMed
Abstract

Insights

Targeting the glycolytic enzyme PFKFB3 with PFK158 effectively eliminates cancer stem cells (CSCs) in malignant pleural mesothelioma (MPM). This approach disrupts key stemness pathways, offering a new strategy against this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Malignant pleural mesothelioma (MPM) is an aggressive cancer often developing chemoresistance.
  • Cancer stem cells (CSCs) contribute to chemoresistance by regulating stemness and cell cycle.
  • Metabolic pathways in CSCs enable treatment evasion through dormancy or proliferation.

Purpose of the Study:

  • To investigate the role of the glycolytic enzyme PFKFB3 in MPM.
  • To evaluate the anticancer effects of PFKFB3 inhibition on CSCs in MPM.
  • To explore PFKFB3 as a therapeutic target for MPM.

Main Methods:

  • Utilized cellular and biochemical assays to study PFKFB3.
  • Employed genetic knockdown and pharmacological inhibition (PFK158) of PFKFB3.
  • Assessed in vitro and in vivo anticancer effects targeting CSCs in MPM models.

Main Results:

  • PFKFB3 inhibition (genetic and PFK158) disrupted the FAK-Stat3-SOX2 nexus.
  • Observed a decrease in stem cell markers (ALDH, CD133, CD44, SOX2) upon PFKFB3 inhibition.
  • PFKFB3 inhibition led to nuclear accumulation of p21 and p27 by decreasing SKP2.
  • PFK158 treatment reduced tumor-initiating cells (TICs) in vivo MPM xenografts.

Conclusions:

  • PFKFB3 is a critical regulator of CSC maintenance in MPM.
  • Targeting PFKFB3 with small molecules like PFK158 shows promise for blocking TICs in MPM.
  • This study provides mechanistic insights for developing novel targeted therapies against MPM CSCs.

More Related Videos

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening07:18

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening

Published on: May 12, 2017

6.5K
A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery07:20

A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery

Published on: February 28, 2020

10.0K

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...
7.0K
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
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.3K
Stem Cell Niche01:26

Stem Cell Niche

The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
5.3K
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.9K