HERC1 Regulates Breast Cancer Cells Migration and Invasion
Tumor cell migration and invasion into adjacent tissues is one of the hallmarks of cancer and the first step towards secondary tumors formation, which represents the leading cause of cancer-related deaths. This process is considered an unmet clinical need in the treatment of this disease, particular...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-03-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/13/6/1309 |
_version_ | 1797541361815126016 |
---|---|
author | Fabiana Alejandra Rossi Ezequiel Hernán Calvo Roitberg Juliana Haydeé Enriqué Steinberg Molishree Umesh Joshi Joaquín Maximiliano Espinosa Mario Rossi |
author_facet | Fabiana Alejandra Rossi Ezequiel Hernán Calvo Roitberg Juliana Haydeé Enriqué Steinberg Molishree Umesh Joshi Joaquín Maximiliano Espinosa Mario Rossi |
author_sort | Fabiana Alejandra Rossi |
collection | DOAJ |
description | Tumor cell migration and invasion into adjacent tissues is one of the hallmarks of cancer and the first step towards secondary tumors formation, which represents the leading cause of cancer-related deaths. This process is considered an unmet clinical need in the treatment of this disease, particularly in breast cancers characterized by high aggressiveness and metastatic potential. To identify and characterize genes with novel functions as regulators of tumor cell migration and invasion, we performed a genetic loss-of-function screen using a shRNA library directed against the Ubiquitin Proteasome System (UPS) in a highly invasive breast cancer derived cell line. Among the candidates, we validated HERC1 as a gene regulating cell migration and invasion. Furthermore, using animal models, our results indicate that HERC1 silencing affects primary tumor growth and lung colonization. Finally, we conducted an in silico analysis using publicly available protein expression data and observed an inverse correlation between HERC1 expression levels and breast cancer patients’ overall survival. Altogether, our findings demonstrate that HERC1 might represent a novel therapeutic target for the development or improvement of breast cancer treatment. |
first_indexed | 2024-03-10T13:13:54Z |
format | Article |
id | doaj.art-d64b35e828d64a3a9957f923cfe44053 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T13:13:54Z |
publishDate | 2021-03-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-d64b35e828d64a3a9957f923cfe440532023-11-21T10:33:14ZengMDPI AGCancers2072-66942021-03-01136130910.3390/cancers13061309HERC1 Regulates Breast Cancer Cells Migration and InvasionFabiana Alejandra Rossi0Ezequiel Hernán Calvo Roitberg1Juliana Haydeé Enriqué Steinberg2Molishree Umesh Joshi3Joaquín Maximiliano Espinosa4Mario Rossi5Instituto de Medicina Traslacional (IIMT), CONICET-Universidad Austral, Pilar, B1629AHJ Buenos Aires, ArgentinaInstituto de Medicina Traslacional (IIMT), CONICET-Universidad Austral, Pilar, B1629AHJ Buenos Aires, ArgentinaInstituto de Medicina Traslacional (IIMT), CONICET-Universidad Austral, Pilar, B1629AHJ Buenos Aires, ArgentinaFunctional Genomics Facility, University of Colorado School of Medicine, Aurora, CO 80045, USAFunctional Genomics Facility, University of Colorado School of Medicine, Aurora, CO 80045, USAInstituto de Medicina Traslacional (IIMT), CONICET-Universidad Austral, Pilar, B1629AHJ Buenos Aires, ArgentinaTumor cell migration and invasion into adjacent tissues is one of the hallmarks of cancer and the first step towards secondary tumors formation, which represents the leading cause of cancer-related deaths. This process is considered an unmet clinical need in the treatment of this disease, particularly in breast cancers characterized by high aggressiveness and metastatic potential. To identify and characterize genes with novel functions as regulators of tumor cell migration and invasion, we performed a genetic loss-of-function screen using a shRNA library directed against the Ubiquitin Proteasome System (UPS) in a highly invasive breast cancer derived cell line. Among the candidates, we validated HERC1 as a gene regulating cell migration and invasion. Furthermore, using animal models, our results indicate that HERC1 silencing affects primary tumor growth and lung colonization. Finally, we conducted an in silico analysis using publicly available protein expression data and observed an inverse correlation between HERC1 expression levels and breast cancer patients’ overall survival. Altogether, our findings demonstrate that HERC1 might represent a novel therapeutic target for the development or improvement of breast cancer treatment.https://www.mdpi.com/2072-6694/13/6/1309HERC1invasionbreastcancertarget |
spellingShingle | Fabiana Alejandra Rossi Ezequiel Hernán Calvo Roitberg Juliana Haydeé Enriqué Steinberg Molishree Umesh Joshi Joaquín Maximiliano Espinosa Mario Rossi HERC1 Regulates Breast Cancer Cells Migration and Invasion Cancers HERC1 invasion breast cancer target |
title | HERC1 Regulates Breast Cancer Cells Migration and Invasion |
title_full | HERC1 Regulates Breast Cancer Cells Migration and Invasion |
title_fullStr | HERC1 Regulates Breast Cancer Cells Migration and Invasion |
title_full_unstemmed | HERC1 Regulates Breast Cancer Cells Migration and Invasion |
title_short | HERC1 Regulates Breast Cancer Cells Migration and Invasion |
title_sort | herc1 regulates breast cancer cells migration and invasion |
topic | HERC1 invasion breast cancer target |
url | https://www.mdpi.com/2072-6694/13/6/1309 |
work_keys_str_mv | AT fabianaalejandrarossi herc1regulatesbreastcancercellsmigrationandinvasion AT ezequielhernancalvoroitberg herc1regulatesbreastcancercellsmigrationandinvasion AT julianahaydeeenriquesteinberg herc1regulatesbreastcancercellsmigrationandinvasion AT molishreeumeshjoshi herc1regulatesbreastcancercellsmigrationandinvasion AT joaquinmaximilianoespinosa herc1regulatesbreastcancercellsmigrationandinvasion AT mariorossi herc1regulatesbreastcancercellsmigrationandinvasion |