scholarly journals Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

2019 ◽  
Vol 20 (12) ◽  
pp. 3080 ◽  
Author(s):  
Fan Wu ◽  
Robert D. McCuaig ◽  
Christopher R. Sutton ◽  
Abel H. Y. Tan ◽  
Yoshni Jeelall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Her2 Positive ◽  
Pathway Gene ◽  
Dual Specificity ◽  
The Brain

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

scholarly journals Effects of Cancer Stem Cells in Triple-Negative Breast Cancer and Brain Metastasis: Challenges and Solutions

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2122
Author(s):  
Kha-Liang Lee ◽  
Gao Chen ◽  
Tai-Yuan Chen ◽  
Yung-Che Kuo ◽  
Yu-Kai Su
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Brain Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Success ◽  
Xenograft Model ◽  
Disease Heterogeneity ◽  
The Brain

A higher propensity of developing brain metastasis exists in triple-negative breast cancer (TNBC). Upon comparing the metastatic patterns of all breast cancer subtypes, patients with TNBC exhibited increased risks of the brain being the initial metastatic site, early brain metastasis development, and shortest brain metastasis-related survival. Notably, the development of brain metastasis differs from that at other sites owing to the brain-unique microvasculature (blood brain barrier (BBB)) and intracerebral microenvironment. Studies of brain metastases from TNBC have revealed the poorest treatment response, mostly because of the relatively backward strategies to target vast disease heterogeneity and poor brain efficacy. Moreover, TNBC is highly associated with the existence of cancer stem cells (CSCs), which contribute to circulating cancer cell survival before BBB extravasation, evasion from immune surveillance, and plasticity in adaptation to the brain-specific microenvironment. We summarized recent literature regarding molecules and pathways and reviewed the effects of CSC biology during the formation of brain metastasis in TNBC. Along with the concept of individualized cancer therapy, certain strategies, namely the patient-derived xenograft model to overcome the lack of treatment-relevant TNBC classification and techniques in BBB disruption to enhance brain efficacy has been proposed in the hope of achieving treatment success.

scholarly journals The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1212
Author(s):  
Getinet M. Adinew ◽  
Equar Taka ◽  
Patricia Mendonca ◽  
Samia S. Messeha ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Option ◽  
Mesenchymal Transition ◽  
Anticancer Effects

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

Cytokeratin 7, GATA3, and SOX-10 is a Comprehensive Panel in Diagnosing Triple Negative Breast Cancer Brain Metastases

2021 ◽  
pp. 106689692199071
Author(s):  
Eric Statz ◽  
Julie M. Jorns
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Tumor ◽  
Cytokeratin 7 ◽  
Breast Cancer Metastases ◽  
Her2 Breast Cancer ◽  
Cancer Metastases ◽  
Breast Cancer Brain Metastasis ◽  
The Brain

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.

scholarly journals MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jhih-Kai Pan ◽  
Cheng-Han Lin ◽  
Yao-Lung Kuo ◽  
Luo-Ping Ger ◽  
Hui-Chuan Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Survival Outcomes ◽  
Poor Survival ◽  
Breast Cancer Brain Metastasis ◽  
High Level

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

scholarly journals Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Mutation Frequency ◽  
Triple Negative ◽  
Genetic Difference ◽  
Her2 Positive ◽  
Ki 67 ◽  
Hormone Receptor Positive ◽  
Somatic Alteration

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.

Distinct MR Imaging Features of Triple-Negative Breast Cancer with Brain Metastasis

2014 ◽  
Vol 25 (3) ◽  
pp. 474-481 ◽  
Author(s):  
Ren-Hua Yeh ◽  
Jyh-Cherng Yu ◽  
Chi-Hong Chu ◽  
Ching-Liang Ho ◽  
Hung-Wen Kao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Mr Imaging ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Imaging Features

scholarly journals CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nataliia Petruk ◽  
Sanni Tuominen ◽  
Malin Åkerfelt ◽  
Jesse Mattsson ◽  
Jouko Sandholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Lung Metastases ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Cell Protrusion

AbstractCD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition.

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