27-hydroxycholesterol induces invasion and migration of breast cancer cells by increasing MMP9 and generating EMT through activation of STAT-3

Publication date: Available online 10 February 2017 Source:Environmental Toxicology and Pharmacology Author(s): Zhaoxia Shen, Dongmei Zhu, Jiao Liu, Juan Chen, Yun Liu, Chunyan Hu, Zhong Li, Yuan Li Breast carcinoma plays a vital role in the reasons of global women's death. ER-related invasion and migration play an important part in the development and prognosis of breast cancer. Here, we found that 27-Hydroxycholesterol (27HC) could induce epithelial-mesenchymal transition (EMT) and increase the expression of the matrix metalloproteinase 9 (MMP9) at mRNA level and the active form. Meanwhile, interestingly, we found 27HC activated signal transducer and activator of transcription 3 (STAT-3) in ER positive cells except activation of ER signaling. Furthermore, inhibition of STAT-3 by siRNA attenuated the 27HC-induced improvement of MMP9 and decreased the invasion and migration ability in MCF7 and T47D cells. In addition, 27HC could also promote MMP9, vimentin and active STAT-3 in the ER negative cells MDA-MB-231. All these results not only raise a mechanism whereby 27HC enhances the invasion and metastasis, but also is helpful to realize 27HC as a potential endogenous detrimental factor in breast tumor patients. Graphical abstract
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research

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Contributors : Timothy Marsh ; Hugo Gonzalez ; Zena Werb ; Jayanta DebnathSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAutophagy is implicated in promoting the metastatic potential of tumor cells. Utilizing a mouse model of mammary cancer to temporally delete essential autophagy regulators, ATG12 or ATG5, in tumor cells during distinct stages of carcinoma progression, we determine a stage-specific role for autophagy in suppressing metastatic colonization. In stark contrast to the tumor-promoting role of autophagy in primary mammary tumors, autophagy restricts colonization of dissem...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Conclusions: STCs with epithelial-like morphology contribute to breast cancer metastasis and represent an attractive model for studying mechanisms of metastatic seeding. The assessment of STCs in histological sections of breast tumors can be a simple and effective method for the prediction of metastasis risk.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionIn leukemic cells the pyrimidine catabolism induces terminal differentiation towards monocytic lineage to check the aberrant cell proliferation whereas in some solid tumors (such as triple negative breast cancer and hepatocellular carcinoma) catalytic degradation of pyrimidines maintains the mesenchymal-like state driven by epithelial to mesenchymal transition (EMT). This review further broadens this concept to understand the effect of PyM on metastasis and, ultimately, delivers a rationale to investigate the involvement of the pyrimidine molecules as oncometabolites. Overall, understanding the non-proliferative ...
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
Mittal Miller The mechanisms that drive ductal carcinoma in situ (DCIS) progression to invasive cancer are not clear. Studying DCIS progression in humans is challenging and not ethical, thus necessitating the characterization of an animal model that faithfully resembles human disease. We have characterized a canine model of spontaneous mammary DCIS and invasive cancer that shares histologic, molecular, and diagnostic imaging characteristics with DCIS and invasive cancer in women. The purpose of the study was to identify markers and altered signaling pathways that lead to invasive cancer and shed light on early m...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
RARITAN, N.J., February 3, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today multiple data presentations from a robust solid tumor portfolio that will be featured at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, taking place February 13-15 in San Francisco. Company-sponsored data presentations will include clinical results for ERLEADA® (apalutamide) and niraparib in prostate cancer; and BALVERSA™ (erdafitinib) in bladder cancer. “We are committed to improving outcomes in patients with prostate and bladder cancer where high unmet ...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
The GATA-type zinc finger transcription factor TRPS1 has been implicated in breast cancer. However, its precise role remains unclear, as both amplifications and inactivating mutations in TRPS1 have been reported. Here, we used in vitro and in vivo loss-of-function approaches to dissect the role of TRPS1 in mammary gland development and invasive lobular breast carcinoma, which is hallmarked by functional loss of E-cadherin. We show that TRPS1 is essential in mammary epithelial cells, since TRPS1-mediated suppression of interferon signaling promotes in vitro proliferation and lactogenic differentiation. Similarly, TRPS1 expr...
Source: Genes and Development - Category: Genetics & Stem Cells Authors: Tags: Research Papers Source Type: research
Immunohistochemistry (IHC) of ER, PR, and Ki-67 are routinely used assays in breast cancer diagnostics. Determination of the proportion of stained cells (labeling index) should be restricted on malignant epithelial cells, carefully avoiding tumor infiltrating stroma and inflammatory cells. Here, we developed a deep learning based digital mask for automated epithelial cell detection using fluoro-chromogenic cytokeratin-Ki-67 double staining and sequential hematoxylin-IHC staining as training material. A partially pre-trained deep convolutional neural network was fine-tuned using image batches from 152 patient samples of inv...
Source: IEE Transactions on Medical Imaging - Category: Biomedical Engineering Source Type: research
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Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Pathol Source Type: research
Publication date: Available online 24 January 2020Source: Arabian Journal of ChemistryAuthor(s): Fabiana L. Silva, Raquel V.S. Silva, Paola C. Branco, Letícia V. Costa-Lotufo, Cynthia Murakami, Maria C.M. Young, Débora A. Azevedo, Paulo R.H. MorenoAbstractCinnamomum stenophyllum (Meisn.) Vattimo-Gil (Lauraceae) is a native and vulnerable Brazilian species restricted to the Atlantic Forest. The leaf essential oil obtained by hydrodistillation was characterized for the first time by two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS). This analysis resulted in the tentat...
Source: Arabian Journal of Chemistry - Category: Chemistry Source Type: research
Targeted therapy using monoclonal antibodies conjugated to toxins is gaining space in the treatment of cancer. Here, we report the anti-tumor effect of a new antibody drug conjugate (ADC) delivering a HDAC inhibitor to ErbB2+ solid tumors. Trastuzumab was partially reduced with tris [2-carboxyethyl] phosphine (TCEP) and conjugated to ST7464AA1, the active form of the prodrug HDAC inhibitor ST7612AA1, through a maleimide-thiol linker to obtain the Antibody Drug Conjugate (ADC) ST8176AA1. The average drug/antibody ratio (DAR) was 4.5 as measured by hydrophobic interaction chromatography (HIC). Binding of ST8176AA1 to ErbB2 r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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