scholarly journals RASSF1C oncogene elicits amoeboid invasion, cancer stemness and invasive EVs via a novel SRC/Rho axis

2021 ◽  
Author(s):  
Maria Laura Tognoli ◽  
Nikola Vlahov ◽  
Sander Steenbeek ◽  
Anna M. Grawenda ◽  
Michael Eyres ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Metastasis ◽  
Early Stage ◽  
Methylation Status ◽  
Target Cells ◽  
Stem Cell Markers ◽  
Breast Cancer Patients ◽  
Actomyosin Contractility ◽  
Amoeboid Cells

AbstractCell plasticity is a crucial hallmark leading to cancer metastasis. Upregulation of Rho/ROCK pathway drives actomyosin contractility, protrusive forces and contributes to the occurrence of highly invasive amoeboid cells in tumors. Cancer stem cells are similarly associated with metastasis, but how these populations arise in tumors is not fully understood. Here we show that the novel oncogene RASSF1C drives mesenchymal to amoeboid transition and stem cell attributes in breast cancer cells. Mechanistically, RASSF1C activates Rho/ROCK via SRC mediated RhoGDI inhibition, resulting in generation of actomyosin contractility. Moreover, we demonstrate that amoeboid cells display the cancer stem cell markers CD133, ALDH1 and the pluripotent marker Nanog; are accompanied by higher invasive potential in vitro and in vivo; and employ extracellular vesicles to transfer the invasive phenotype to target cells and tissue. Importantly, the underlying RASSF1C driven biological processes concur to explain clinical data: namely, methylation of the RASSF1C promoter correlates with better survival in early stage breast cancer patients. Therefore, we propose the use of RASSF1 gene promoter methylation status as a biomarker for patient stratification.

scholarly journals The Jumonji Domain-Containing Histone Demethylase Homolog 1D/lysine Demethylase 7A (JHDM1D/KDM7A) Is an Epigenetic Activator of RHOJ Transcription in Breast Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Ziyu Zhang ◽  
Baoyu Chen ◽  
Yuwen Zhu ◽  
Tianyi Zhang ◽  
Yibiao Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Rna Polymerase Ii ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Methylation Status ◽  
Small Gtpase ◽  
Epigenetic Mechanism ◽  
Migration And Invasion ◽  
Breast Cancer Patients

The small GTPase RHOJ is a key regulator of breast cancer metastasis by promoting cell migration and invasion. The prometastatic stimulus TGF-β activates RHOJ transcription via megakaryocytic leukemia 1 (MKL1). The underlying epigenetic mechanism is not clear. Here, we report that MKL1 deficiency led to disrupted assembly of the RNA polymerase II preinitiation complex on the RHOJ promoter in breast cancer cells. This could be partially explained by histone H3K9/H3K27 methylation status. Further analysis confirmed that the H3K9/H3K27 dual demethylase JHDM1D/KDM7A was essential for TGF-β-induced RHOJ transcription in breast cancer cells. MKL1 interacted with and recruited KDM7A to the RHOJ promoter to cooperatively activate RHOJ transcription. KDM7A knockdown attenuated migration and invasion of breast cancer cells in vitro and mitigated the growth and metastasis of breast cancer cells in nude mice. KDM7A expression level, either singularly or in combination with that of RHOJ, could be used to predict prognosis in breast cancer patients. Of interest, KDM7A appeared to be a direct transcriptional target of TGF-β signaling. A SMAD2/SMAD4 complex bound to the KDM7A promoter and mediated TGF-β-induced KDM7A transcription. In conclusion, our data unveil a novel epigenetic mechanism whereby TGF-β regulates the transcription of the prometastatic small GTPase RHOJ. Screening for small-molecule inhibitors of KDM7A may yield effective therapeutic solutions to treat malignant breast cancers.

scholarly journals Optimizing Silanization to Functionalize Stainless Steel Wire: Towards Breast Cancer Stem Cell Isolation

Materials ◽  
2020 ◽  
Vol 13 (17) ◽  
pp. 3693
Author(s):  
Aliya Bekmurzayeva ◽  
Kanat Dukenbayev ◽  
Helena S. Azevedo ◽  
Enrico Marsili ◽  
Daniele Tosi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stainless Steel ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Breast Cancer Stem Cell ◽  
Target Cells ◽  
Specific Cell ◽  
Stem Cell Markers ◽  
In Vitro Test ◽  
Steel Wires

Chemically modified metal surfaces have been used to recognize and capture specific cell types and biomolecules. In this work, stainless steel wires were functionalized with aptamers against breast cancer stem cell markers. Stainless steel wires were first electropolished and silanized via electrodeposition. Aptamers were then attached to the silanized surface through a cross-linker. The functionalized wires were able to capture the target cells in an in vitro test. During surface modification steps, wires were analyzed by atomic force microscopy, cyclic voltammetry, scanning electron and fluorescence microscopy to determine their surface composition and morphology. Optimized conditions of silanization (applied potential, solution pH, heat treatment temperature) for obtaining an aptamer-functionalized wire were determined in this work together with the use of several surface characterization techniques suitable for small-sized and circular wires. These modified wires have potential applications for the in vivo capture of target cells in blood flow, since their small size allows their insertion as standard guidewires in biomedical devices.

scholarly journals Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Natalia Krawczyk ◽  
Franziska Meier-Stiegen ◽  
Malgorzata Banys ◽  
Hans Neubauer ◽  
Eugen Ruckhaeberle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Current Data ◽  
Stem Cell Markers ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Evaluation and characterization of circulating tumor cells (CTCs) have become a major focus of translational cancer research. Presence of CTCs predicts worse clinical outcome in early and metastatic breast cancer. Whether all cells from the primary tumor have potential to disseminate and form subsequent metastasis remains unclear. As part of the metastatic cascade, tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to enter blood circulation. During EMT epithelial antigens are downregulated; thus, such tumor cells might elude classical epithelial marker-based detection. Several researchers postulated that some CTCs express stem cell-like phenotype; this might lead to chemoresistance and enhanced metastatic potential of such cells. In the present review, we discuss current data on EMT and stem cell markers in CTCs of breast cancer and their clinical significance.

Breast cancer and incidence of non-caseating granulomas diagnosed in PET avid chest lymphadenopahy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12549-e12549
Author(s):  
Rabih Bechara ◽  
Patricia Rich ◽  
Christopher Parks ◽  
Dacian Bonta ◽  
Ioana Bonta
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Cancer Metastasis ◽  
Early Stage ◽  
Lung Parenchyma ◽  
Breast Cancer Metastasis ◽  
Current Treatment ◽  
Endobronchial Ultrasound ◽  
Breast Cancer Patients ◽  
Caseating Granuloma

e12549 Background: Breast cancer is known to metastasize to the lung parenchyma and lymph nodes. Most breast malignancies are clinically staged using radiographic modalities (e.g. PET scans). Importantly, several inflammatory disorders will present lymph node FDG-uptake on PET, which can be mistaken for breast cancer metastasis. This may alter staging and implicitly treatment for individuals within whom both undiagnosed autoimmune disorders and breast cancer co-occur. We aim to examine the frequency of non-caseating granulomas diagnosed in PET avid mediastinal/hilar nodes in patients with known breast cancer. Methods: Between March 2013 and December 2015, 46 women diagnosed with breast cancer were staged by PET-CT. Those with positive result in the mediastinum/hilum underwent linear endobronchial ultrasound (EBUS) for pathologic diagnosis and ensuing treatment Results: Of the 46 patients with avid mediastinal/hilar adenopathy, 31 (67%) had malignant cytology on EBUS; the remaining 15 had positive PET but negative cytology for malignancy. Twelve of the 15 patients with false positive PET had reactive lymph nodes, and 3 had non-caseating granulomas on cytology (see table). Twenty percent of the patients with negative cytology and positive PET had non-caseating granuloma, and 6.5 % of all patients with positive PET had non-caseating granulomas. Conclusions: To our knowledge, this study represents the largest cohort of breast cancer patients, where the incidence of non-caseating granulomas is investigated in PET-positive mediastinal/hilar nodes. We conclude that in selected patients, in addition to imaging, pathologic staging should be done. Also, the finding of non-caseating granulomas in these patients may either indicate an incidental diagnosis of early stage sarcoidosis, or an inflammatory reaction to the current treatment (sarcomatoid reaction). We also suggest that these patients should be followed for any manifestations of sarcoidosis. [Table: see text]

scholarly journals Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Abhishek Tyagi ◽  
Sambad Sharma ◽  
Kerui Wu ◽  
Shih-Ying Wu ◽  
Fei Xing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Early Stage ◽  
Critical Role ◽  
Smoking History ◽  
Lipocalin 2 ◽  
Breast Cancer Patients ◽  
Metastatic Niche ◽  
Increased Risk

AbstractSmoking has a profound impact on tumor immunity, and nicotine, which is the major addictive component of smoke, is known to promote tumor progression despite being a non-carcinogen. In this study, we demonstrate that chronic exposure of nicotine plays a critical role in the formation of pre-metastatic niche within the lungs by recruiting pro-tumor N2-neutrophils. This pre-metastatic niche promotes the release of STAT3-activated lipocalin 2 (LCN2), a secretory glycoprotein from the N2-neutrophils, and induces mesenchymal-epithelial transition of tumor cells thereby facilitating colonization and metastatic outgrowth. Elevated levels of serum and urine LCN2 is elevated in early-stage breast cancer patients and cancer-free females with smoking history, suggesting that LCN2 serve as a promising prognostic biomarker for predicting increased risk of metastatic disease in female smoker(s). Moreover, natural compound, salidroside effectively abrogates nicotine-induced neutrophil polarization and consequently reduced lung metastasis of hormone receptor-negative breast cancer cells. Our findings suggest a pro-metastatic role of nicotine-induced N2-neutrophils for cancer cell colonization in the lungs and illuminate the therapeutic use of salidroside to enhance the anti-tumor activity of neutrophils in breast cancer patients.

scholarly journals Circulating MicroRNAs and Blood-Brain-Barrier Function in Breast Cancer Metastasis

2020 ◽  
Vol 26 (13) ◽  
pp. 1417-1427 ◽  
Author(s):  
Carolin J. Curtaz ◽  
Constanze Schmitt ◽  
Kinga G. Blecharz-Lang ◽  
Norbert Roewer ◽  
Achim Wöckel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Brain Barrier ◽  
Target Cells ◽  
Breast Cancer Patients ◽  
Blood Brain ◽  
The Brain

Brain metastases are a major cause of death in breast cancer patients. A key event in the metastatic progression of breast cancer in the brain is the migration of cancer cells across the blood-brain barrier (BBB). The BBB is a natural barrier with specialized functions that protect the brain from harmful substances, including antitumor drugs. Extracellular vesicles (EVs) sequestered by cells are mediators of cell-cell communication. EVs carry cellular components, including microRNAs that affect the cellular processes of target cells. Here, we summarize the knowledge about microRNAs known to play a significant role in breast cancer and/or in the BBB function. In addition, we describe previously established in vitro BBB models, which are a useful tool for studying molecular mechanisms involved in the formation of brain metastases.

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