Integrin β3 Reprogramming Stemness in HER2-Positive Breast Cancer Cell Lines
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View abstract on PubMed
Summary
This summary is machine-generated.Integrin αVβ3 (ITGβ3) drives stemness and trastuzumab resistance in HER2-positive breast cancer. Inhibiting ITGβ3 with cilengitide may overcome treatment resistance by reducing stem cell markers.
Area Of Science
- Oncology
- Molecular Biology
- Cell Biology
Background
- HER2-positive breast cancer exhibits aggressive behavior and poor prognosis.
- Trastuzumab resistance develops in about 50% of patients within a year, necessitating alternative therapeutic strategies.
Purpose Of The Study
- To investigate the role of Integrin αVβ3 (ITGβ3) in promoting stemness and trastuzumab resistance in HER2-positive breast cancer.
- To explore the potential of targeting ITGβ3 to overcome trastuzumab resistance.
Main Methods
- Utilized HER2-positive breast cancer cell lines (HCC1954 and SKBR3) with chronic trastuzumab exposure.
- Assessed stem cell marker expression, ITGβ3 overexpression, and ITGβ3 silencing.
- Investigated the Notch signaling pathway activation and the effect of combining trastuzumab with cilengitide (an integrin inhibitor).
Main Results
- Trastuzumab exposure upregulated multiple stem cell markers.
- ITGβ3 overexpression enhanced stem cell marker expression, while ITGβ3 silencing reduced it, confirming ITGβ3's role in maintaining stemness and resistance.
- ITGβ3 was found to activate the Notch signaling pathway.
- Combined treatment with trastuzumab and cilengitide significantly decreased stem cell markers in resistant cells.
Conclusions
- ITGβ3 plays a critical role in mediating stemness and trastuzumab resistance in HER2-positive breast cancer.
- ITGβ3 mediates resistance through the Notch signaling pathway.
- Targeting ITGβ3 with integrin inhibitors like cilengitide represents a promising therapeutic strategy to enhance trastuzumab efficacy and overcome resistance.
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