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Published on: October 27, 2020
SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the
Ariana Acevedo-Díaz1, Beatriz M Morales-Cabán2, Astrid Zayas-Santiago3
1Department of Biology, University of Puerto Rico, Bayamón, PR 00959, USA.
Abstract:
Triple-negative breast cancer (TNBC) is the most aggressive, metastatic, and lethal breast cancer subtype. To improve the survival of TNBC patients, it is essential to explore new signaling pathways for the further development of effective drugs. This study aims to investigate the role of the secretory carrier membrane protein 3 (SCAMP3) in TNBC and its association with the epidermal growth factor receptor (EGFR). Through an internalization assay, we demonstrated that SCAMP3 colocalizes and redistributes EGFR from the cytoplasm to the perinucleus. Furthermore, SCAMP3 knockout decreased proliferation, colony and tumorsphere formation, cell migration, and invasion of TNBC cells. Immunoblots and degradation assays showed that SCAMP3 regulates EGFR through its degradation. In addition, SCAMP3 modulates AKT, ERK, and STAT3 signaling pathways. TNBC xenograft models showed that SCAMP3 depletion delayed tumor cell proliferation at the beginning of tumor development and modulated the expression of genes from the PDGF pathway. Additionally, analysis of TCGA data revealed elevated SCAMP3 expression in breast cancer tumors. Finally, patients with TNBC with high expression of SCAMP3 showed decreased RFS and DMFS. Our findings indicate that SCAMP3 could contribute to TNBC development through the regulation of multiple pathways and has the potential to be a target for breast cancer therapy.
Insights
Secretory carrier membrane protein 3 (SCAMP3) drives aggressive triple-negative breast cancer (TNBC) by regulating epidermal growth factor receptor (EGFR) signaling. Targeting SCAMP3 may offer a new therapeutic strategy for TNBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Identifying novel molecular targets is crucial for improving TNBC patient outcomes.
Purpose of the Study:
- To investigate the role of secretory carrier membrane protein 3 (SCAMP3) in TNBC.
- To explore the association between SCAMP3 and epidermal growth factor receptor (EGFR) in TNBC.
Main Methods:
- Internalization assays to study SCAMP3-EGFR colocalization.
- SCAMP3 knockout in TNBC cells to assess proliferation, migration, and invasion.
- Immunoblotting and degradation assays to analyze EGFR regulation.
- TNBC xenograft models and TCGA data analysis.
Main Results:
- SCAMP3 colocalizes with and redistributes EGFR, promoting its degradation.
- SCAMP3 depletion reduces TNBC cell proliferation, migration, and invasion.
- SCAMP3 modulates AKT, ERK, STAT3, and PDGF signaling pathways.
- Elevated SCAMP3 expression correlates with decreased relapse-free survival (RFS) and distant metastasis-free survival (DMFS) in TNBC patients.
Conclusions:
- SCAMP3 plays a significant role in TNBC development and progression.
- SCAMP3 regulates key signaling pathways implicated in cancer.
- SCAMP3 represents a potential therapeutic target for TNBC.
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