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CD147 mediates chemoresistance in breast cancer via ABCG2 by affecting its cellular localization and dimerization
Shuangyuan Zhou1, Liqiu Liao, Chen Chen
1Department of Dermatology, XiangYa Hospital, Central South University, Changsha, Hunan 410008, China.
Abstract:
CD147 and ABCG2 both have been reported to mediate Multidrug resistance (MDR) in breast cancer. Recent study demonstrates that CD147 could form a complex with ABCG2 on the cell membrane in primary effusion lymphoma. However, whether these two molecules regulate each other in breast cancer and result in MDR is not clear. We established four MCF-7 cell lines transfected with CD147 and/or ABCG2 and found that CD147 could increase the expression and dimerization of ABCG2, affect its cellular localization and regulate its drug transporter function. The findings derived from cells were confirmed subsequently in clinic samples of chemotherapy-sensitive/resistant breast cancer.
Insights
CD147 protein enhances ABCG2 expression and function, contributing to multidrug resistance (MDR) in breast cancer. This interaction was confirmed in both cell lines and clinical samples, revealing a new mechanism for chemotherapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multidrug resistance (MDR) is a significant challenge in breast cancer treatment.
- Both CD147 and ABCG2 (ATP-binding cassette sub-family G member 2) are implicated in MDR.
- The interaction between CD147 and ABCG2 in breast cancer and its role in MDR remain unclear.
Purpose of the Study:
- To investigate the regulatory relationship between CD147 and ABCG2 in breast cancer.
- To determine if CD147 influences ABCG2 expression, localization, and function.
- To elucidate the role of the CD147-ABCG2 complex in mediating breast cancer multidrug resistance.
Main Methods:
- Transfection of MCF-7 breast cancer cell lines with CD147 and/or ABCG2.
- Analysis of ABCG2 expression, dimerization, and cellular localization.
- Assessment of ABCG2 drug transporter function.
- Validation of findings in clinical samples from chemotherapy-sensitive and resistant breast cancer patients.
Main Results:
- CD147 significantly increased the expression and dimerization of ABCG2 in MCF-7 cells.
- CD147 altered the cellular localization of ABCG2.
- CD147 modulated the drug transporter activity of ABCG2.
- These cellular findings were corroborated in clinical breast cancer samples.
Conclusions:
- CD147 plays a crucial role in regulating ABCG2 in breast cancer.
- The CD147-ABCG2 interaction contributes to the development of multidrug resistance in breast cancer.
- Targeting the CD147-ABCG2 pathway may offer a novel strategy to overcome chemotherapy resistance in breast cancer.
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