Related Experiment Video

Updated: May 1, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

7.2K

DLC1 suppresses NF-κB activity in prostate cancer cells due to its stabilizing effect on adherens junctions

Veenu Tripathi1, Nicholas C Popescu1, Drazen B Zimonjic1

  • 1Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4262, Bethesda, Maryland 20892 USA.

Springerplus
|April 1, 2014
PubMed

Insights

The Deleted in Liver Cancer 1 (DLC1) gene suppresses tumor growth in prostate cancer by inhibiting NF-κB signaling. DLC1 reduces cell proliferation and metastasis, offering potential therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • The Deleted in Liver Cancer 1 (DLC1) gene encodes a RhoGTPase-activating protein (RhoGAP) with tumor suppressor functions.
  • Rho GTPases are involved in NF-κB activation, impacting prostate carcinoma (PCA) cell proliferation, survival, and metastasis.

Purpose of the Study:

  • To investigate the role of DLC1 in regulating NF-κB activity in highly metastatic prostate cancer.
  • To elucidate the mechanisms by which DLC1 influences NF-κB signaling and its downstream effects.

Main Methods:

  • Transduction of DLC1 in androgen-independent, metastatic PCA cell lines.
  • Assessment of NF-κB activity, IκBα phosphorylation, ubiquitination, and degradation.
  • Analysis of NF-κB-mediated gene expression.
  • Evaluation of calcium dependency and adherens junction stabilization.

Main Results:

  • DLC1 transduction negatively regulated NF-κB activity in a GAP- and α-catenin-dependent manner.
  • DLC1 suppressed IκBα phosphorylation, promoted its cytoplasmic relocation, and attenuated its degradation.
  • DLC1-mediated NF-κB suppression reduced the expression of NF-κB target genes.
  • These effects were calcium-dependent and linked to DLC1-mediated stabilization of adherens junctions.

Conclusions:

  • DLC1 acts as a suppressor of NF-κB signaling in metastatic prostate cancer.
  • DLC1's tumor-suppressive function is mediated through RhoGAP activity and calcium-dependent adherens junction stabilization.
  • DLC1 represents a potential therapeutic target for prostate cancer treatment.
Keywords:
Adherens junction (AJ)DLC1NF-kBProstate cancerRho

More Related Videos

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells13:38

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Published on: January 18, 2017

9.7K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

7.7K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.6K
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
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.0K
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...
8.6K
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
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.0K