Related Experiment Video
Updated: Feb 19, 2026
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
CD146, a novel target of CD44-signaling, suppresses breast tumor cell invasion
Allal Ouhtit1, Mohammed E Abdraboh2, Andrew D Hollenbach3
1Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar. aouhtit@qu.edu.qa.
Background:
We have previously validated three novel CD44-downstream positively regulated transcriptional targets, including Cortactin, Survivin and TGF-β2, and further characterized the players underlying their separate signaling pathways. In the present study, we identified CD146 as a potential novel target, negatively regulated by CD44. While the exact function of CD146 in breast cancer (BC) is not completely understood, substantial evidence from our work and others support the hypothesis that CD146 is a suppressor of breast tumor progression.
Methods:
Therefore, using molecular and pharmacological approaches both in vitro and in breast tissues of human samples, the present study validated CD146 as a novel target of CD44-signaling suppressed during BC progression.
Results:
Our results revealed that CD44 activation could cause a substantial decrease of CD146 expression with an equally notable converse effect upon CD44-siRNA inhibition. More interestingly, activation of CD44 decreased cellular CD146 and increased soluble CD146 through CD44-dependent activation of MMP.
Conclusion:
Here, we provide a possible mechanism by which CD146 suppresses BC progression as a target of CD44-downstream signaling, regulating neovascularization and cancer cell motility.
Insights
CD44 signaling suppresses CD146, a novel target, in breast cancer (BC) progression. This study reveals CD146 acts as a tumor suppressor by regulating BC cell motility and neovascularization.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- CD44 is a known regulator in breast cancer (BC) progression.
- Previous work identified CD44-downstream targets Cortactin, Survivin, and TGF-β2.
- CD146's role in BC is under investigation, with evidence suggesting it suppresses tumor progression.
Purpose of the Study:
- To validate CD146 as a novel CD44-signaling target suppressed during BC progression.
- To elucidate the regulatory relationship between CD44 and CD146 in BC.
- To understand the mechanism by which CD146 influences BC progression.
Main Methods:
- Utilized molecular and pharmacological approaches.
- Conducted in vitro experiments.
- Analyzed human breast tissue samples.
Main Results:
- CD44 activation significantly decreased CD146 expression.
- CD44 inhibition (using siRNA) led to increased CD146 expression.
- CD44 activation modulated both cellular and soluble CD146 levels via MMP activation.
Conclusions:
- CD146 is a novel, negatively regulated target of CD44 signaling in BC.
- CD146 acts as a suppressor of breast tumor progression.
- CD146 influences BC progression by regulating neovascularization and cancer cell motility.
