Diana Gulei1, Nikolay Mehterov2, Hui Ling3, Giorgio Stanta4, Cornelia Braicu5, Ioana Berindan-Neagoe6. 1. MEDFUTURE-Research Center for Advanced Medicine, University of Medicine and Farmacy Iuliu-Hatieganu, Marinescu 23 Street, Cluj-Napoca, Romania. Electronic address: diana.gulei@umfcluj.ro. 2. Department of Medical Biology, Medical University Plovdiv, Vasil Aprilov 15-А Street, Plovdiv, Bulgaria; Technological Center for Emergency Medicine, Vasil Aprilov 15-А Street, Plovdiv, Bulgaria. 3. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. 4. Department of Medical Sciences, University of Trieste, Fiume 447 Street, Trieste, Italy. 5. Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street, No. 23, 400337 Cluj-Napoca, Romania. Electronic address: cornelia.braicu@umfcluj.ro. 6. MEDFUTURE-Research Center for Advanced Medicine, University of Medicine and Farmacy Iuliu-Hatieganu, Marinescu 23 Street, Cluj-Napoca, Romania; Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. Ion Chiricuta", Republicii 34-36 Street, Cluj-Napoca, Romania; Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street, No. 23, 400337 Cluj-Napoca, Romania. Electronic address: ioana.neagoe@umfcluj.ro.
Abstract
BACKGROUND: Lack of early diagnosis methods and the development of drug resistance are among the main reasons for increased mortality rates within breast cancer patients. These two aspects are governed by specific pro-carcinogenic modifications, where TGBβ-induced EMT is one of the leading actors. Endowment of the epithelial cells with mesenchymal characteristics allows them to migrate and invade secondary tissues in order to form malignant sites and also confers chemoresistance. TGFβ which role switches from the tumor suppressor cytokine to the oncogenic one favoring the tumor microenvironment regulates this process. SCOPE OF REVIEW: This review aims to comprehensively present the updated TGFβ-induced EMT in breast cancer, including the regulatory role of the non-coding RNAs with focus on the miR-200 family and newly discovered lncRNAs such as HOTAIRM1. Additionally, a new phenotype, P-EMT, also modulated by miR-200 and miR-34 families that form complex feedback loops with TGFβ, SNAI1 and ZEB1/2 is presented under an updated form. MAJOR CONCLUSIONS: The hallmarks of EMT are becoming increasingly associated with aggressive forms of breast cancer and low survival rates among patients. Considering that this phenotypical switch can trigger drug resistance, invasion and metastasis, inhibition of EMT could represent an important milestone in mammary cancer treatment. GENERAL SIGNIFICANCE: The present review assembles the most recent data regarding TGFβ induced EMT, including the input of non-coding RNAs, contributing to the possible development of new targeted treatment strategies for cancer patients.
BACKGROUND: Lack of early diagnosis methods and the development of drug resistance are among the main reasons for increased mortality rates within breast cancerpatients. These two aspects are governed by specific pro-carcinogenic modifications, where TGBβ-induced EMT is one of the leading actors. Endowment of the epithelial cells with mesenchymal characteristics allows them to migrate and invade secondary tissues in order to form malignant sites and also confers chemoresistance. TGFβ which role switches from the tumor suppressor cytokine to the oncogenic one favoring the tumor microenvironment regulates this process. SCOPE OF REVIEW: This review aims to comprehensively present the updated TGFβ-induced EMT in breast cancer, including the regulatory role of the non-coding RNAs with focus on the miR-200 family and newly discovered lncRNAs such as HOTAIRM1. Additionally, a new phenotype, P-EMT, also modulated by miR-200 and miR-34 families that form complex feedback loops with TGFβ, SNAI1 and ZEB1/2 is presented under an updated form. MAJOR CONCLUSIONS: The hallmarks of EMT are becoming increasingly associated with aggressive forms of breast cancer and low survival rates among patients. Considering that this phenotypical switch can trigger drug resistance, invasion and metastasis, inhibition of EMT could represent an important milestone in mammary cancer treatment. GENERAL SIGNIFICANCE: The present review assembles the most recent data regarding TGFβ induced EMT, including the input of non-coding RNAs, contributing to the possible development of new targeted treatment strategies for cancerpatients.
Authors: Christian Fischer; Christian Reiner; Gerhard Schmidmaier; Julian Doll; Christopher Child; Paul Alfred Grützner; Bahram Biglari; Sonja Boxriker; Arash Moghaddam Journal: Ther Clin Risk Manag Date: 2018-04-16 Impact factor: 2.423