Related Experiment Video

Updated: Feb 7, 2026

Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
07:57

Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors

Published on: January 20, 2023

6.8K

Simvastatin functions as a heat shock protein 90 inhibitor against triple-negative breast cancer

Xinhui Kou1,2, Xiaoxiao Jiang2, Huijuan Liu2

  • 1Department of Endocrine and Department of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

Cancer Science
|July 25, 2018
PubMed

Insights

Acetylation at K292 in heat shock protein 90 (Hsp90) drives breast cancer progression. Targeting this site with simvastatin and LBH589 offers a novel therapeutic strategy for triple-negative breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Heat shock protein 90 (Hsp90) acetylation regulates chaperone activity crucial for malignant transformation.
  • Identifying functional acetylation sites on Hsp90 is key for developing novel anticancer drugs.

Purpose of the Study:

  • To investigate the role of K292 acetylation in Hsp90α in breast cancer development and treatment.
  • To validate K292-acetylated Hsp90 as an anticancer drug target.
  • To explore the therapeutic potential of combining simvastatin and LBH589 for triple-negative breast cancer.

Main Methods:

  • Investigated the impact of K292 acetylation on Hsp90 affinity for ATP, cochaperones, and client proteins.
  • Assessed the effects of K292 acetylation on cancer cell proliferation, migration, and invasion in vitro.
  • Evaluated tumor growth in vivo using a mouse xenograft model.
  • Examined the mechanism of action of simvastatin and LBH589 on Hsp90 acetylation and client maturation.

Main Results:

  • Acetylation at K292 in Hsp90α enhances Hsp90 binding to ATP, cochaperones, and client proteins, promoting cancer progression.
  • K292-acetylated Hsp90 is a viable drug target, with disruption of the Hsp90/Cdc37 complex leading to client degradation.
  • Simvastatin inhibits K292-acetylated Hsp90/Cdc37 complex formation, while LBH589 promotes Hsp90 cycling.
  • Combination therapy with simvastatin and LBH589 increased apoptosis in a triple-negative breast cancer xenograft model.

Conclusions:

  • Acetylation at K292 of Hsp90α is critical for breast cancer progression and represents a promising therapeutic target.
  • Simvastatin acts as a novel Hsp90 inhibitor by disrupting the K292-acetylated Hsp90/Cdc37 complex.
  • The combination of simvastatin and LBH589 presents a novel therapeutic strategy for triple-negative breast cancer.
Keywords:
Cdc37Hsp90LBH589acetylationsimvastatin

More Related Videos

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

18.9K
Author Spotlight: Exploring Heat Shock Proteins in Malaria and Tuberculosis Infections07:14

Author Spotlight: Exploring Heat Shock Proteins in Malaria and Tuberculosis Infections

Published on: March 8, 2024

1.9K

Related Concept Videos

Structural Protein Function01:56

Structural Protein Function

Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity.  In bones and teeth, it mineralizes to...
30.0K
Responses to Heat and Cold Stress02:45

Responses to Heat and Cold Stress

Every organism has an optimum temperature range within which healthy growth and physiological functioning can occur. At the ends of this range, there will be a minimum and maximum temperature that interrupt biological processes.
14.9K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
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
Mechanical Protein Functions01:58

Mechanical Protein Functions

Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force. 
5.7K
Gram-negative Bacterial Protein Secretion Systems01:17

Gram-negative Bacterial Protein Secretion Systems

Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
978