Related Experiment Video

Updated: May 6, 2026

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
11:13

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

Published on: June 9, 2023

2.3K

The KLK5 protease suppresses breast cancer by repressing the mevalonate pathway

Georgios Pampalakis1, Osahon Obasuyi, Olga Papadodima

  • 1Department of Pharmacy, University of Patras, Rion-Patras 26500.

Oncotarget
|October 26, 2013
PubMed

Insights

Reintroducing Kallikrein-related peptidase 5 (KLK5) in breast cancer cells suppressed malignancy by altering cholesterol metabolism and reducing active RhoA. This protease may offer a novel therapeutic strategy for breast cancer treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Kallikrein-related peptidase 5 (KLK5) is aberrantly expressed in various cancers, but its functional role remains unclear.
  • Understanding KLK5's function is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the functional role of KLK5 in breast cancer.
  • To elucidate the molecular mechanisms by which KLK5 affects cancer malignancy.

Main Methods:

  • Reconstitution of KLK5 expression in MDA-MB-231 breast cancer cells.
  • Analysis of epithelial-mesenchymal transition (EMT) gene expression.
  • Assessment of mevalonate pathway gene expression and cholesterol metabolism.
  • Measurement of active RhoA levels and isoprenoid synthesis.
  • In vitro and in vivo assays to evaluate cancer malignancy.

Main Results:

  • KLK5 re-expression dose-dependently suppressed breast cancer cell malignancy in vitro and in vivo.
  • KLK5 suppressed key EMT genes and altered mevalonate pathway gene expression, mimicking cholesterol starvation.
  • KLK5 reduced cellular cholesterol and fatty acid synthesis, enhanced LDL-cholesterol uptake, and diminished active RhoA levels.
  • Restoration of active RhoA via geranylgeranyl pyrophosphate reversed the anti-malignancy effects of KLK5.

Conclusions:

  • KLK5 suppresses breast cancer malignancy by modulating the mevalonate pathway and reducing active RhoA signaling.
  • This study suggests a novel mechanism for protease-mediated cancer suppression.
  • KLK5 represents a potential therapeutic target for breast cancer treatment.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

19.0K
A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

331

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

4.3K
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...
4.0K
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
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
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...
7.1K