Files and links (1)
Published, Version of Record (VoR)CC BY-NC-ND V4.0, Open
Journal article
Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity
Neoplasia (New York, N.Y.), v 16(12), pp 1047-1058
Dec 2014
PMID: 25499218
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone.
Metrics
Details
- Title
- Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity
- Creators
- Giovanna Ferrari-Amorotti - University of Modena and Reggio EmiliaClaudia Chiodoni - Fondazione IRCCS Istituto Nazionale dei TumoriFei Shen - Drexel UniversitySara Cattelani - University of Modena and Reggio EmiliaAngela Rachele Soliera - University of Modena and Reggio EmiliaGloria Manzotti - University of Modena and Reggio EmiliaGiulia Grisendi - Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell’Adulto, Modena, ItalyMassimo Dominici - Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell’Adulto, Modena, ItalyFrancesco Rivasi - University of Modena and Reggio EmiliaMario Paolo Colombo - Fondazione IRCCS Istituto Nazionale dei TumoriAlessandro Fatatis - Drexel UniversityBruno Calabretta - Kimmel Cancer Center
- Publication Details
- Neoplasia (New York, N.Y.), v 16(12), pp 1047-1058
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000347172100006
- Scopus ID
- 2-s2.0-85003394010
- Other Identifier
- 991019168264804721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology