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

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.

Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer

“…miRNAs could suppress gene expression at both transcriptional and posttranscriptional level by binding to complementary sequences of its target mRNA 17 . miRNAs serve as a crucial components in epigenetic modification for many important biological pathways including EMT 18 . Previous research has suggested that miR-337-3p could regulate the EMT process during cancer progression and metastasis 19 .…”

Shikonin inhibits migration and invasion of triple-negative breast cancer cells by suppressing epithelial-mesenchymal transition via miR-17-5p/PTEN/Akt pathway

“…EMT is defined as the loss of epithelial phenotypes and the gain of mesenchymal characteristics [5]. These changes endow cancer cells with higher metastatic capacity and contribute to abnormal cellular growth, differentiation and drug resistance [6]. Some signaling pathways are previously reported to be involved in EMT, such as transforming growth factor-β (TGF-β), cadherin, Notch, Wnt/β-catenin, and GATA [2,7,8].…”

Nilotinib, a Discoidin domain receptor 1 (DDR1) inhibitor, induces apoptosis and inhibits migration in breast cancer

“…Breast cancer is the most common type of malignancy in women and is the second leading cause of female cancer mortality in the world [1][2][3]. Recent reports have revealed that breast cancer is responsible for 6% of the total 7.5 million cancer mortalities worldwide [3,4]. Although numerous advanced diagnostic and therapeutic methods have been used in the treatment of breast cancer, but its metastasis is still the primary cause of death [5,6].…”