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New Insights into the Implication of Epigenetic Alterations in the EMT of Triple Negative Breast Cancer

Laboratoire d’Oncologie Moléculaire, Centre Jean PERRIN et IMoST, UMR 1240, Inserm/Université Clermont Auvergne 58 rue Montalembert, 63000 Clermont-Ferrand, France
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Cancers 2019, 11(4), 559; https://doi.org/10.3390/cancers11040559
Received: 5 February 2019 / Revised: 22 March 2019 / Accepted: 11 April 2019 / Published: 18 April 2019
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Abstract

Breast cancer is the most common cancer and leading cause of cancer death among women worldwide, encompassing a wide heterogeneity of subtypes with different clinical features. During the last two decades, the use of targeted therapies has emerged in clinical research in order to increase treatment efficiency, improve prognosis and reduce recurrence. However, the triple negative breast cancer (TNBC) subtype remains a clinical challenge, with poor prognosis since no therapeutic targets have been identified. This aggressive breast cancer entity lacks expression of oestrogen receptor (ER) and progesterone receptor (PR), and it does not overexpress human epidermal growth factor receptor 2 (HER2). The major reason for TNBC poor prognosis is early therapeutic escape from conventional treatments, leading to aggressive metastatic relapse. Metastases occur after an epithelial-mesenchymal transition EMT of epithelial cells, allowing them to break free from the primary tumour site and to colonize distant organs. Cancer-associated EMT consists not only of acquired migration and invasion ability, but involves complex and comprehensive reprogramming, including changes in metabolism, expression levels and epigenetic. Recently, many studies have considered epigenetic alterations as the primary initiator of cancer development and metastasis. This review builds a picture of the epigenetic modifications implicated in the EMT of breast cancer. It focuses on TNBC and allows comparisons with other subtypes. It emphasizes the role of the main epigenetic modifications lncRNAs, miRNAs, histone and DNA- modifications in tumour invasion and appearance of metastases. These epigenetic alterations can be considered biomarkers representing potential diagnostic and prognostic factors in order to define a global metastatic signature for TNBC. View Full-Text
Keywords: triple negative breast cancer TNBC; epithelial-mesenchymal transition EMT; epigenetic modifications; long non-coding RNAs LncRNAs; miRNAs; histone modifications; DNA methylation; metastasis triple negative breast cancer TNBC; epithelial-mesenchymal transition EMT; epigenetic modifications; long non-coding RNAs LncRNAs; miRNAs; histone modifications; DNA methylation; metastasis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Khaled, N.; Bidet, Y. New Insights into the Implication of Epigenetic Alterations in the EMT of Triple Negative Breast Cancer. Cancers 2019, 11, 559.

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