Profilin-1 overexpression restores adherens junctions in MDA-MB-231 breast cancer cells in R-cadherin-dependent manner

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.

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Rb Suppresses Collective Invasion, Circulation and Metastasis of Breast Cancer Cells in CD44-Dependent Manner

PLoS ONE ◽

10.1371/journal.pone.0080590 ◽

2013 ◽

Vol 8 (12) ◽

pp. e80590 ◽

Cited By ~ 14

Author(s):

Kui-Jin Kim ◽

Alzbeta Godarova ◽

Kari Seedle ◽

Min-Ho Kim ◽

Tan A. Ince ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Dependent Manner ◽

Collective Invasion

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ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11

Cancers ◽

10.3390/cancers13174293 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4293

Author(s):

Xiaowen Liu ◽

Manuel A. Riquelme ◽

Yi Tian ◽

Dezhi Zhao ◽

Francisca M. Acosta ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Bone Metastasis ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cells ◽

Cxcr4 Expression ◽

Dependent Manner ◽

Cancer Cell Migration ◽

Dose Dependent

ATP released by bone osteocytes is shown to activate purinergic signaling and inhibit the metastasis of breast cancer cells into the bone. However, the underlying molecular mechanism is not well understood. Here, we demonstrate the important roles of the CXCR4 and P2Y11 purinergic receptors in mediating the inhibitory effect of ATP on breast cancer cell migration and bone metastasis. Wound-healing and transwell migration assays showed that non-hydrolysable ATP analogue, ATPγS, inhibited migration of bone-tropic human breast cancer cells in a dose-dependent manner. BzATP, an agonist for P2X7 and an inducer for P2Y11 internalization, had a similar dose-dependent inhibition on cell migration. Both ATPγS and BzATP suppressed the expression of CXCR4, a chemokine receptor known to promote breast cancer bone metastasis, and knocking down CXCR4 expression by siRNA attenuated the inhibitory effect of ATPγS on cancer cell migration. While a P2X7 antagonist A804598 had no effect on the impact of ATPγS on cell migration, antagonizing P2Y11 by NF157 ablated the effect of ATPγS. Moreover, the reduction in P2Y11 expression by siRNA decreased cancer cell migration and abolished the impact of ATPγS on cell migration and CXCR4 expression. Similar to the effect of ATPγS on cell migration, antagonizing P2Y11 inhibited bone-tropic breast cancer cell migration in a dose-dependent manner. An in vivo study using an intratibial bone metastatic model showed that ATPγS inhibited breast cancer growth in the bone. Taken together, these results suggest that ATP inhibits bone-tropic breast cancer cells by down-regulating the P2Y11 purinergic receptor and the down-regulation of CXCR4 expression.

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Poly-ADP-Ribosylation of Estrogen Receptor-Alpha by PARP1 Mediates Antiestrogen Resistance in Human Breast Cancer Cells

Cancers ◽

10.3390/cancers11010043 ◽

2019 ◽

Vol 11 (1) ◽

pp. 43 ◽

Cited By ~ 2

Author(s):

Nicholas Pulliam ◽

Jessica Tang ◽

Weini Wang ◽

Fang Fang ◽

Riddhi Sood ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Estrogen Receptor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Target Genes ◽

Tamoxifen Resistance ◽

Tamoxifen Treatment ◽

Dependent Manner ◽

Tamoxifen Resistant

Therapeutic targeting of estrogen receptor-α (ERα) by the anti-estrogen tamoxifen is standard of care for premenopausal breast cancer patients and remains a key component of treatment strategies for postmenopausal patients. While tamoxifen significantly increases overall survival, tamoxifen resistance remains a major limitation despite continued expression of ERα in resistant tumors. Previous reports have described increased oxidative stress in tamoxifen resistant versus sensitive breast cancer and a role for PARP1 in mediating oxidative damage repair. We hypothesized that PARP1 activity mediated tamoxifen resistance in ERα-positive breast cancer and that combining the antiestrogen tamoxifen with a PARP1 inhibitor (PARPi) would sensitize tamoxifen resistant cells to tamoxifen therapy. In tamoxifen-resistant vs. -sensitive breast cancer cells, oxidative stress and PARP1 overexpression were increased. Furthermore, differential PARylation of ERα was observed in tamoxifen-resistant versus -sensitive cells, and ERα PARylation was increased by tamoxifen treatment. Loss of ERα PARylation following treatment with a PARP inhibitor (talazoparib) augmented tamoxifen sensitivity and decreased localization of both ERα and PARP1 to ERα-target genes. Co-administration of talazoparib plus tamoxifen increased DNA damage accumulation and decreased cell survival in a dose-dependent manner. The ability of PARPi to overcome tamoxifen resistance was dependent on ERα, as lack of ERα-mediated estrogen signaling expression and showed no response to tamoxifen-PARPi treatment. These results correlate ERα PARylation with tamoxifen resistance and indicate a novel mechanism-based approach to overcome tamoxifen resistance in ER+ breast cancer.

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Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

Cancer Nanotechnology ◽

10.1186/s12645-019-0052-1 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Natalia Lemos Chaves ◽

Danilo Aquino Amorim ◽

Cláudio Afonso Pinho Lopes ◽

Irina Estrela-Lopis ◽

Julia Böttner ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Breast Cancer Cells ◽

Human Tumor ◽

Metastatic Breast ◽

Cytotoxic Action ◽

Dependent Manner ◽

Metastatic Cells ◽

Mcf 7

Abstract Background Nanocarriers have the potential to improve the therapeutic index of currently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period. The association of maghemite nanoparticles (NPs) with rhodium citrate (forming the complex hereafter referred to as MRC) has the potential to increase the specificity of the cytotoxic action of the latter compound, since this nanocomposite can be guided or transported to a target by the use of an external magnetic field. However, the behavior of these nanoparticles for an extended time of exposure to breast cancer cells has not yet been explored, and nor has MRC cytotoxicity comparison in different cell lines been performed until now. In this work, the effects of MRC NPs on these cells were analyzed for up to 72 h of exposure, and we focused on comparing NPs’ therapeutic effectiveness in different cell lines to elect the most responsive model, while elucidating the underlying action mechanism. Results MRC complexes exhibited broad cytotoxicity on human tumor cells, mainly in the first 24 h. However, while MRC induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability at 48 and 72 h, MCF-7 appears to recover its viability after 48 h of exposure. The recovery of MCF-7 is possibly explained by a resistance mechanism mediated by PGP (P-glycoprotein) proteins, which increase in these cells after MRC treatment. Remaining viable tumor metastatic cells had the migration capacity reduced after treatment with MRC (24 h). Moreover, MRC treatment induced S phase arrest of the cell cycle. Conclusion MRC act at the nucleus, inhibiting DNA synthesis and proliferation and inducing cell death. These effects were verified in both tumor lines, but MDA-MB-231 cells seem to be more responsive to the effects of NPs. In addition, NPs may also disrupt the metastatic activity of remaining cells, by reducing their migratory capacity. Our results suggest that MRC nanoparticles are a promising nanomaterial that can provide a convenient route for tumor targeting and treatment, mainly in metastatic cells.

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Identification of drivers of breast cancer invasion by secretome analysis: insight into CTGF signaling

Scientific Reports ◽

10.1038/s41598-020-74838-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Johanna W. Hellinger ◽

Franziska Schömel ◽

Judith V. Buse ◽

Christof Lenz ◽

Gerd Bauerschmitz ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Cancer Cells ◽

Cell Invasion ◽

Transforming Growth Factor Beta ◽

Breast Cancer Cells ◽

Transforming Growth Factor ◽

Tissue Growth ◽

Dependent Manner ◽

Mesenchymal Transition

Abstract An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion. Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.

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SGK3 Is an Estrogen-Inducible Kinase Promoting Estrogen-Mediated Survival of Breast Cancer Cells

Molecular Endocrinology ◽

10.1210/me.2010-0294 ◽

2011 ◽

Vol 25 (1) ◽

pp. 72-82 ◽

Cited By ~ 35

Author(s):

Yuanzhong Wang ◽

Dujin Zhou ◽

Sheryl Phung ◽

Selma Masri ◽

David Smith ◽

...

Keyword(s):

Breast Cancer ◽

Protein Kinase ◽

Cell Survival ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Dependent Manner ◽

Binding Regions ◽

Er Positive ◽

Mcf 7 ◽

Positive Breast Cancer

Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a protein kinase of the AGC family of protein kinase A, protein kinase G, and protein kinase C and functions downstream of phosphatidylinositol 3-kinase (PI3K). Recent study revealed that SGK3 plays a pivotal role in Akt/protein kinase B independent signaling downstream of oncogenic PI3KCA mutations in breast cancer. Here we report that SGK3 is an estrogen receptor (ER) transcriptional target and promotes estrogen-mediated cell survival of ER-positive breast cancer cells. Through a meta-analysis on 22 microarray studies of breast cancer in the Oncomine database, we found that the expression of SGK3 is significantly higher (5.7-fold, P < 0.001) in ER-positive tumors than in ER-negative tumors. In ER-positive breast cancer cells, SGK3 expression was found to be induced by 17β-estradiol (E2) in a dose- and time-dependent manner, and the induction of SGK3 mRNA by E2 is independent of newly synthesized proteins. We identified two ERα-binding regions at the sgk3 locus through chromatin immunoprecipitation with massively parallel DNA sequencing. Promoter analysis revealed that ERα stimulates the activity of sgk3 promoters by interaction with these two ERα-binding regions on E2 treatment. Loss-of-function analysis indicated that SGK3 is required for E2-mediated cell survival of MCF-7 breast carcinoma cells. Moreover, overexpression of SGK3 could partially protect MCF-7 cells against apoptosis caused by antiestrogen ICI 182,780. Together, our study defines the molecular mechanism of regulation of SGK3 by estrogen/ER and provides a new link between the PI3K pathway and ER signaling as well as a new estrogen-mediated cell survival mechanism mediated by SGK3 in breast cancer cells.

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A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo

Cells ◽

10.3390/cells9020362 ◽

2020 ◽

Vol 9 (2) ◽

pp. 362 ◽

Cited By ~ 6

Author(s):

Fairouz Sioud ◽

Souheila Amor ◽

Imène ben Toumia ◽

Aida Lahmar ◽

Virginie Aires ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Protective Action ◽

Dependent Manner ◽

4T1 Breast Cancer ◽

Induced Apoptosis ◽

Cellular Modifications

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.

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Cytotoxic, Anti-Migration, and Anti-Invasion Activities on Breast Cancer Cells of Angucycline Glycosides Isolated from a Marine-Derived Streptomyces sp.

Marine Drugs ◽

10.3390/md17050277 ◽

2019 ◽

Vol 17 (5) ◽

pp. 277 ◽

Cited By ~ 5

Author(s):

Xin-Ying Qu ◽

Jin-Wei Ren ◽

Ai-Hong Peng ◽

Shi-Qi Lin ◽

Dan-Dan Lu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Ring Cleavage ◽

Migration And Invasion ◽

Dependent Manner ◽

Streptomyces Sp ◽

Deoxy Sugar ◽

Ic50 Values ◽

Dose Dependent

Four angucycline glycosides were previously characterized from marine-derived Streptomyces sp. OC1610.4. Further investigation of this strain cultured on different fermentation media from that used previously resulted in the isolation of two new angucycline glycosides, vineomycins E and F (1–2), and five known homologues, grincamycin L (3), vineomycinone B2 (4), fridamycin D (5), moromycin B (7), and saquayamycin B1 (8). Vineomycin F (2) contains an unusual ring-cleavage deoxy sugar. All the angucycline glycosides isolated from Streptomyces sp. OC1610.4 were evaluated for their cytotoxic activity against breast cancer cells MCF-7, MDA-MB-231, and BT-474. Moromycin B (7), saquayamycin B1 (8), and saquayamycin B (9) displayed potent anti-proliferation against the tested cell lines, with IC50 values ranging from 0.16 to 0.67 μM. Saquayamycin B (9) inhibited the migration and invasion of MDA-MB-231 cells in a dose-dependent manner, as detected by Transwell and wound-healing assays.

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Toxicological Effects of Traumatic Acid and Selected Herbicides on Human Breast Cancer Cells: In Vitro Cytotoxicity Assessment of Analyzed Compounds

Molecules ◽

10.3390/molecules24091710 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1710 ◽

Cited By ~ 4

Author(s):

Agata Jabłońska-Trypuć ◽

Urszula Wydro ◽

Elżbieta Wołejko ◽

Andrzej Butarewicz

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Dependent Manner ◽

Food Contaminants ◽

Food Ingredient ◽

Concentration Dependent Manner ◽

Traumatic Acid

The main consequence of herbicides use is the presence of their residues in food of plant origin. A growing body of evidence indicates that herbicides cause detrimental effects upon human health while demonstrating a direct link of pesticides exposure with the occurrence of human chronic diseases, including cancer. There is a pressing need to develop our knowledge regarding interactions of food contaminants and food components both in vitro and in vivo. Pesticides are highly undesirable food contaminants, and traumatic acid (TA) is a very beneficial food ingredient, therefore we decided to study if TA may act as a compound that delays the stimulatory effect of pesticides on breast cancer cells. To analyze the potential effects that selected herbicides (MCPA, mesotrione, bifenox and dichlobenil) may have upon cancerous cells, we conducted studies of the cytotoxicity of physiological concentrations of four pesticides and the mix of TA with tested herbicides in three different breast cancer cell lines (MCF-7, ZR-75-1 and MDA-MB-231) and one normal healthy breast cell line MCF-12A. Based on the obtained results we conclude that TA in a concentration-dependent manner might influence selected effects of the studied herbicides for particular cancer cells lines.

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