SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways
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 secret...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/11/2807 |
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| author | Ariana Acevedo-Díaz Beatriz M. Morales-Cabán Astrid Zayas-Santiago Michelle M. Martínez-Montemayor Ivette J. Suárez-Arroyo |
| author_facet | Ariana Acevedo-Díaz Beatriz M. Morales-Cabán Astrid Zayas-Santiago Michelle M. Martínez-Montemayor Ivette J. Suárez-Arroyo |
| author_sort | Ariana Acevedo-Díaz |
| collection | DOAJ |
| description | 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 <i>PDGF</i> 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. |
| first_indexed | 2024-03-10T01:25:50Z |
| format | Article |
| id | doaj.art-61596beccf914df3b4c592bb342215c4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:25:50Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-61596beccf914df3b4c592bb342215c42023-11-23T13:51:30ZengMDPI AGCancers2072-66942022-06-011411280710.3390/cancers14112807SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling PathwaysAriana Acevedo-Díaz0Beatriz M. Morales-Cabán1Astrid Zayas-Santiago2Michelle M. Martínez-Montemayor3Ivette J. Suárez-Arroyo4Department of Biology, University of Puerto Rico, Bayamón, PR 00959, USADepartment of Biochemistry, School of Medicine, Universidad Central del Caribe, Bayamón, PR 00960, USADepartment of Pathology, School of Medicine, Universidad Central del Caribe, Bayamón, PR 00960, USADepartment of Biochemistry, School of Medicine, Universidad Central del Caribe, Bayamón, PR 00960, USADepartment of Biochemistry, School of Medicine, Universidad Central del Caribe, Bayamón, PR 00960, USATriple-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 <i>PDGF</i> 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.https://www.mdpi.com/2072-6694/14/11/2807SCAMP3triple-negative breast cancerEGFRERKPDGFSTAT3 |
| spellingShingle | Ariana Acevedo-Díaz Beatriz M. Morales-Cabán Astrid Zayas-Santiago Michelle M. Martínez-Montemayor Ivette J. Suárez-Arroyo SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways Cancers SCAMP3 triple-negative breast cancer EGFR ERK PDGF STAT3 |
| title | SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways |
| title_full | SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways |
| title_fullStr | SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways |
| title_full_unstemmed | SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways |
| title_short | SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways |
| title_sort | scamp3 regulates egfr and promotes proliferation and migration of triple negative breast cancer cells through the modulation of akt erk and stat3 signaling pathways |
| topic | SCAMP3 triple-negative breast cancer EGFR ERK PDGF STAT3 |
| url | https://www.mdpi.com/2072-6694/14/11/2807 |
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