Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix

Zolota, Vasiliki; Tzelepi, Vassiliki; Piperigkou, Zoi; Kourea, Helen P.; Papakonstantinou, Efthymia; Αργέντου, Μαρία-Ιωάννα; Karamanos, Nikos K.

doi:10.3390/cancers13040713

Cited by 47 publications

(18 citation statements)

References 98 publications

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“…This type of cell transformation is associated with chemical and morphological variations. Particularly regarding breast cancer (mainly TNBC), current data suggests that its initiation and progression may be associated to epigenetic alterations (such as DNA methylation or chromatin remodelling) [ 17 , 21 ]. Recent studies have focused on the biophysics of the cancer state, shedding a new light on carcinogenesis beyond the recognised biochemical and genetic variations associated to malignancy.…”

Section: Introductionmentioning

confidence: 99%

Who’s Who? Discrimination of Human Breast Cancer Cell Lines by Raman and FTIR Microspectroscopy

Santos

Martins

Carvalho

et al. 2022

Cancers

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(1) Breast cancer is presently the leading cause of death in women worldwide. This study aims at identifying molecular biomarkers of cancer in human breast cancer cells, in order to differentiate highly aggressive triple-negative from non-triple-negative cancers, as well as distinct triple-negative subtypes, which is currently an unmet clinical need paramount for an improved patient care. (2) Raman and FTIR (Fourier transform infrared) microspectroscopy state-of-the-art techniques were applied, as highly sensitive, specific and non-invasive methods for probing heterogeneous biological samples such as human cells. (3) Particular biochemical features of malignancy were unveiled based on the cells’ vibrational signature, upon principal component analysis of the data. This enabled discrimination between TNBC (triple-negative breast cancer) and non-TNBC, TNBC MSL (mesenchymal stem cell-like) and TNBC BL1 (basal-like 1) and TNBC BL1 highly metastatic and low-metastatic cell lines. This specific differentiation between distinct TNBC subtypes—mesenchymal from basal-like, and basal-like 1 with high-metastatic potential from basal-like 1 with low-metastatic potential—is a pioneer result, of potential high impact in cancer diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

Who’s Who? Discrimination of Human Breast Cancer Cell Lines by Raman and FTIR Microspectroscopy

Santos

Martins

Carvalho

et al. 2022

Cancers

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“…Here we report that the slight EGFR expression is correlated with a robust decrease in ERK1/2 phosphorylation in monoclonal shERb MDA-MB-231 cells, compared to the excessive phosphorylation in the invasive MDA-MB-231 cells. In previous studies, we have demonstrated that the distinct ER status of breast cancer cells is correlated to different microRNA (miRNA) epigenetic signatures and that specific miRNAs (i.e., miR-10b, miR-145 and miR-200b) are possible biomarkers for regulating breast cancer cell behavior by interacting with matrix mediators (19,20,53,54). Especially for ERb, this ER is the epigenetic mediator of miR-10b, miR-145 and miR-92, specific miRNAs implicated in breast cancer progression (19,55).…”

Section: Discussionmentioning

confidence: 99%

ESR2 Drives Mesenchymal-to-Epithelial Transition in Triple-Negative Breast Cancer and Tumorigenesis In Vivo

et al. 2022

Self Cite

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Estrogen receptors (ERs) have pivotal roles in the development and progression of triple-negative breast cancer (TNBC). Interactions among cancer cells and tumor microenvironment are orchestrated by the extracellular matrix that is rapidly emerging as prominent contributor of fundamental processes of breast cancer progression. Early studies have correlated ERβ expression in tumor sites with a more aggressive clinical outcome, however ERβ exact role in the progression of TNBC remains to be elucidated. Herein, we introduce the functional role of ERβ suppression following isolation of monoclonal cell populations of MDA-MB-231 breast cancer cells transfected with shRNA against human ESR2 that permanently resulted in 90% reduction of ERβ mRNA and protein levels. Further, we demonstrate that clone selection results in strongly reduced levels of the aggressive functional properties of MDA-MB-231 cells, by transforming their morphological characteristics, eliminating the mesenchymal-like traits of triple-negative breast cancer cells. Monoclonal populations of shERβ MDA-MB-231 cells undergo universal matrix reorganization and pass on a mesenchymal-to-epithelial transition state. These striking changes are encompassed by the total prevention of tumorigenesis in vivo following ERβ maximum suppression and isolation of monoclonal cell populations in TNBC cells. We propose that these novel findings highlight the promising role of ERβ targeting in future pharmaceutical approaches for managing the metastatic dynamics of TNBC breast cancer.

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“…Negative control: isotype control HSPE, known to modulate these processes. 35,36 Gene expression was determined using qPCR.…”

Section: Syndecan-4 Silencing Leads To Alterations In the Gene Expression Of Adhesion Moleculesmentioning

confidence: 99%

microRNA‐140‐3p modulates invasiveness, motility, and extracellular matrix adhesion of breast cancer cells by targeting syndecan‐4

Onyeisi

Greve

Espinoza-Sánchez

et al. 2021

J of Cellular Biochemistry

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Syndecan-4, a predicted target of the microRNA miR-140-3p, plays an important role in multiple steps of tumor progression and is the second most abundant heparan sulfate proteoglycan produced by breast carcinoma cell lines. To investigate the potential functional relationship of miR-140-3p and syndecan-4, MDA-MB-231, SKBR3, and MCF-7 breast cancer (BC) cells were transiently transfected with pre-miR-140-3p, syndecan-4 small interfering RNAJ, or control reagents, respectively. Altered cell behavior was monitored by adhesion, migration, and invasion chamber assays. Moreover, the prognostic value of syndecan-4 was assessed by Kaplan-Maier Plotter analysis of gene expression data from tumor samples of 4929 patients. High expression of syndecan-4 was associated with better relapse-free survival in the whole collective of BC patients, but correlated with a worse survival in the subgroup of estrogen receptor negative and estrogen/progesterone-receptor negative patients. miR-140-3p expression was associated with improved survival irrespective of hormone receptor status. miR-140-3p overexpression induced posttranscriptional downregulation of syndecan-4, as demonstrated by quantitative real-time PCR (qPCR), flow cytometry, and luciferase assays, resulting in decreased BC cell migration and matrigel invasiveness. Furthermore, miR-140-3p overexpression and syndecan-4 silencing increased the adhesion of BC to fibronectin and laminin. qPCR analysis demonstrated that syndecan-4 silencing leads to altered gene expression of adhesion-related molecules, such as fibronectin and focal adhesion kinase, as well as in the gene expression of the proinvasive factors matrix metalloproteinase 2 and heparanase (also known as HPSE). We conclude that syndecan-4 is a novel target of miR-140-3p that regulates BC cell invasiveness and cell-matrix interactions in the tumor microenvironment.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix

Cited by 47 publications

References 98 publications

Who’s Who? Discrimination of Human Breast Cancer Cell Lines by Raman and FTIR Microspectroscopy

Who’s Who? Discrimination of Human Breast Cancer Cell Lines by Raman and FTIR Microspectroscopy

ESR2 Drives Mesenchymal-to-Epithelial Transition in Triple-Negative Breast Cancer and Tumorigenesis In Vivo

microRNA‐140‐3p modulates invasiveness, motility, and extracellular matrix adhesion of breast cancer cells by targeting syndecan‐4

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