FOXC1 Regulates FGFR1 Isoform Switching to Promote Invasion Following TGF{beta}-Induced EMT

Epithelial-to-mesenchymal transition (EMT) is an important physiologic process that drives tissue formation during development, but also contributes to disease pathogenesis, including fibrosis and cancer metastasis. Elevated expression of the FOXC1 transcription factor has been detected in several metastatic cancers that have undergone EMT. Therefore, mechanistic insight into the role of FOXC1 in the initiation of the EMT process was sought. It was determined that although Foxc1 transcript expression was elevated following TGFβ1-induced EMT of NMuMG cells, FOXC1 was not required for this induction. RNA sequencing revealed that the mRNA levels of FGF receptor 1-isoform IIIc (Fgfr1-IIIc), normally activated upon TGFβ1 treatment, were reduced in Foxc1 knockdown cells, and overexpression of Foxc1 was sufficient to induce Fgfr1-IIIc expression, but not EMT. Chromatin immunoprecipitation experiments demonstrated that FOXC1 binds to an Fgfr1 upstream regulatory region and that FOXC1 activates an Fgfr1 promoter element. Furthermore, elevated expression of Foxc1 led to increased Fgfr1-IIIc transcript. Foxc1 knockdown impaired the FGF2-mediated three-dimensional migratory ability of NMuMG cells, which was rescued by expression of FGFR1. In addition, elevated expression of FOXC1 and FGFR1 was also observed in migratory mesenchymal MDA-MB-231 breast cancer cells. Together, these results define a role for FOXC1 in specifying an invasive mesenchymal cell type by promoting FGFR1 i...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Chromatin, Epigenetics, and RNA Regulation Source Type: research

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rooks Ionising radiation (IR) is commonly used for cancer therapy; however, its potential influence on the metastatic ability of surviving cancer cells exposed directly or indirectly to IR remains controversial. Metastasis is a multistep process by which the cancer cells dissociate from the initial site, invade, travel through the blood stream or lymphatic system, and colonise distant sites. This complex process has been reported to require cancer cells to undergo epithelial-mesenchymal transition (EMT) by which the cancer cells convert from an adhesive, epithelial to motile, mesenchymal form and is also associated wit...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ntamaria-Martinez Rüegg Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSION: HDACi suppress the epithelial-mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells. PMID: 31932908 [PubMed - as supplied by publisher]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Cancer Res Clin Oncol Source Type: research
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Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ConclusionHDACi suppress the epithelial –mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 9 January 2020Source: Stem Cell ReportsAuthor(s): Raghava R. Sunkara, Rahul M. Sarate, Priyanka Setia, Sanket Shah, Sanjay Gupta, Pankaj Chaturvedi, Poonam Gera, Sanjeev K. WaghmareSummaryWnt signaling is involved in the regulation of cancer stem cells (CSCs); however, the molecular mechanism involved is still obscure. SFRP1, a Wnt inhibitor, is downregulated in various human cancers; however, its role in tumor initiation and CSC regulation remains unexplored. Here, we used a skin carcinogenesis model, which showed early tumor initiation in Sfrp1−/− (Sfrp1 knockout) mice and i...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
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Source: Cell Cycle - Category: Cytology Authors: Source Type: research
CONCLUSIONS: The differential diagnosis between OM and primary ovarian cancer can be challenging for the pathologist as well and immunostaining is of help. GCFDP15 is the most specific for breast carcinoma. In contrast with the recent papers published in the literature, we detected TTF-1 cytoplasmic expression in invasive breast carcinoma by SPT24 clone. PMID: 31912104 [PubMed - in process]
Source: Romanian Journal of Morphology and Embryology - Category: General Medicine Tags: Rom J Morphol Embryol Source Type: research
CONCLUSIONS: Taken together, miR-383-5p was downregulated in breast cancer tissues and cell lines, and overexpression of miR-383-5p inhibited cell proliferation, migration, and invasion in breast cancer cells by targeting LDHA. Based on our findings, miR-383-5p may be a prognostic biomarker and therapeutic target for breast cancer. PMID: 31903982 [PubMed - as supplied by publisher]
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
In conclusion, the novel benzofuran scaffold may be a promising lead for the development of potential oestrogen receptor inhibitors. PMID: 31935604 [PubMed - as supplied by publisher]
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research
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