Inhibition of Histone Deacetylases Reverses Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells through a Slug Mediated Mechanism

Rahimian, Aliasghar; Barati, Ghasem; Mehrandish, Reza; Mellati, Ali Awsat

doi:10.1134/s0026893318030111

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…Histone modification inhibitors used in studies evaluating the role of specific histone modification treatments in promoting or inhibiting the EMT of TNBC are listed in a supplementary table (Table 4 and see Figure S1). The mechanisms of treatment of the histone deacetylase inhibitors vorinostat ( SAHA ) [94,112], panobinostat ( LBH589 ) [93], entinostat ( ENT ) [113,114], trichostatin A ( TSA ) [115] and HTPB [116], as well as the lysine demethylase inhibitor parnate ( PCPA ) [117], and the histone methyltransferase inhibitor UNC0638 [118], along with their main role in reversing EMT are listed in Table 4 (see Figure S1).…”

Section: Histone Modificationsmentioning

confidence: 99%

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

Khaled

Bidet

2019

Cancers

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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.

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Section: Histone Modificationsmentioning

confidence: 99%

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

Khaled

Bidet

2019

Cancers

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“…An invasion assay was performed using the thin gel method according to previous studies [41] and the manufacturer's protocol. TransWell hanging inserts (24 wells) were purchased from TC inserts (SARSTEDT) and coated with 35 μL Matrigel matrix.…”

Section: Matrigel Invasion Assaymentioning

confidence: 99%

Role of Cancer Stem-like Cells in the Process of Invasion and Mesenchymal Transformation by a Reconstituted Triple-negative Breast Cancer Cell Population Resistant to p53-induced Apoptosis

Inoue

Imanishi

Kanzaki

et al. 2022

Acta Histochem. Cytochem.

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We investigated the role of cancer stem cells (CSCs) in a population of triple-negative breast cancer (TNBC) cells that are resistant to apoptosis. A human breast cancer cell population capable of inducing p53 expression with doxycycline (Dox) was created and used as an untreated control (UT). After the addition of Dox to UT for 5 days, the cell population reconstituted with cells showing resistance to apoptosis was named RE. Fluorescence-activated cell sorting (FACS) and immunostaining revealed that after the addition of Dox, the ratio of cells in the S and G2/M phases decreased in UT as apoptosis proceeded, but did not markedly change in apoptosis-resistant RE. CSC-like cells in RE exhibited a cell morphology with a larger ratio of the major/minor axis than UT. FACS showed that RE had a higher proportion of CSC-like cells and contained more CD44 + CD24 − mesenchymal CSCs than ALD-H1A3 + epithelial-like CSCs. In a Matrigel invasion assay, UT was more likely to form a threedimensional cell population, whereas RE exhibited a planar population, higher migration ability, and the up-regulated expression of epithelial-mesenchymal transition-related genes. These results provide insights into the mechanisms by which TNBC cells acquire treatment resistance at the time of recurrence.

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“…In cancer this process is usually partial and is associated with metastatic disease and chemoresistance [ 212 ]. Several groups have demonstrated that HDAC inhibitors suppress the EMT transcriptional program in several cancer types, including breast, biliary tract, bladder, and others [ 213 , 214 , 215 , 216 , 217 ]. Importantly, this suppression was evident in cell lines that were predominantly mesenchymal-like, either intrinsically or due to exogenous signals such as TGFβ.…”

Section: Effects Of Hdac Inhibitors and Therapeutic Implications For Tumor Heterogeneitymentioning

confidence: 99%

HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity

Karagiannis

Ράμπιας

2021

Cancers

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Intra-tumoral heterogeneity presents a major obstacle to cancer therapeutics, including conventional chemotherapy, immunotherapy, and targeted therapies. Stochastic events such as mutations, chromosomal aberrations, and epigenetic dysregulation, as well as micro-environmental selection pressures related to nutrient and oxygen availability, immune infiltration, and immunoediting processes can drive immense phenotypic variability in tumor cells. Here, we discuss how histone deacetylase inhibitors, a prominent class of epigenetic drugs, can be leveraged to counter tumor heterogeneity. We examine their effects on cellular processes that contribute to heterogeneity and provide insights on their mechanisms of action that could assist in the development of future therapeutic approaches.

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Inhibition of Histone Deacetylases Reverses Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells through a Slug Mediated Mechanism

Cited by 3 publications

References 31 publications

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

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

Role of Cancer Stem-like Cells in the Process of Invasion and Mesenchymal Transformation by a Reconstituted Triple-negative Breast Cancer Cell Population Resistant to p53-induced Apoptosis

HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity

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