Related Experiment Video

Updated: Mar 20, 2026

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

3.7K

Epigenetic regulation of cell adhesion-mediated drug resistance acquisition in multiple myeloma

Yusuke Furukawa1, Jiro Kikuchi

  • 1Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University.

[Rinsho Ketsueki] the Japanese Journal of Clinical Hematology
|June 7, 2016
PubMed

Insights

This study reveals histone H3 lysine-27 trimethylation (H3K27me3) is key to multiple myeloma drug resistance. Targeting the IGF-1R/PI3K/Akt pathway can reverse resistance by restoring H3K27me3 epigenetic marks.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Cell adhesion-mediated drug resistance (CAM-DR) is a major challenge in multiple myeloma treatment.
  • Epigenetic modifications, particularly histone methylation, play crucial roles in cancer progression and drug resistance.

Purpose of the Study:

  • To elucidate the epigenetic mechanisms driving CAM-DR in multiple myeloma.
  • To identify specific histone modifications and signaling pathways involved in CAM-DR.

Main Methods:

  • Investigated histone H3 lysine-27 trimethylation (H3K27me3) as a critical epigenetic mark.
  • Examined the role of EZH2 phosphorylation and its impact on H3K27me3.
  • Utilized in vitro and in vivo murine myeloma models.
  • Assessed the effect of inhibiting the IGF-1R/PI3K/Akt pathway.

Main Results:

  • Identified H3K27me3 as a critical epigenetic regulator of CAM-DR.
  • Demonstrated that cell adhesion inactivates EZH2 via phosphorylation, preventing H3K27 hypermethylation and sustaining anti-apoptotic gene expression (IGF1, BCL2, HIF1A).
  • Showed that inhibiting the IGF-1R/PI3K/Akt pathway reversed CAM-DR by promoting EZH2 dephosphorylation and H3K27 hypermethylation.

Conclusions:

  • This study provides the first evidence of an epigenetic mechanism underlying CAM-DR in multiple myeloma.
  • Targeting EZH2 phosphorylation through kinase inhibitors offers a potential therapeutic strategy to overcome drug resistance.
  • Combination chemotherapy including kinase inhibitors may enhance the therapeutic index in multiple myeloma treatment.

More Related Videos

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

9.2K
Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis10:04

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis

Published on: May 1, 2015

13.6K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
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...
4.1K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
65
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved...
10.4K