scholarly journals Identification of Cross Talk between FoxM1 and RASSF1A as a Therapeutic Target of Colon Cancer

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 199 ◽  
Author(s):  
Thomas G. Blanchard ◽  
Steven J. Czinn ◽  
Vivekjyoti Banerjee ◽  
Neha Sharda ◽  
Andrea C. Bafford ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Ex Vivo ◽  
Inverse Correlation ◽  
Suppressor Gene ◽  
Akt Inhibitor ◽  
Ex Vivo Model ◽  
Advanced Colon Cancer ◽  
Foxm1 Expression ◽  
First Time

Metastatic colorectal cancer (mCRC) is characterized by the expression of cellular oncogenes, the loss of tumor suppressor gene function. Therefore, identifying integrated signaling between onco-suppressor genes may facilitate the development of effective therapy for mCRC. To investigate these pathways we utilized cell lines and patient derived organoid models for analysis of gene/protein expression, gene silencing, overexpression, and immunohistochemical analyses. An inverse relationship in expression of oncogenic FoxM1 and tumor suppressor RASSF1A was observed in various stages of CRC. This inverse correlation was also observed in mCRC cells lines (T84, Colo 205) treated with Akt inhibitor. Inhibition of FoxM1 expression in mCRC cells as well as in our ex vivo model resulted in increased RASSF1A expression. Reduced levels of RASSF1A expression were found in normal cells (RWPE-1, HBEpc, MCF10A, EC) stimulated with exogenous VEGF165. Downregulation of FoxM1 also coincided with increased YAP phosphorylation, indicative of tumor suppression. Conversely, downregulation of RASSF1A coincided with FoxM1 overexpression. These studies have identified for the first time an integrated signaling pathway between FoxM1 and RASSF1A in mCRC progression, which may facilitate the development of novel therapeutic options for advanced colon cancer therapy.

scholarly journals The tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer

2012 ◽  
Vol 42 (2) ◽  
pp. 676-682 ◽  
Author(s):  
RUI-SI XU ◽  
XIAO-DONG WU ◽  
SI-QI ZHANG ◽  
CHANG-FENG LI ◽  
LEI YANG ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Human Colon ◽  
Suppressor Gene ◽  
Human Colon Cancer ◽  
Novel Target

The NBL1 tumor suppressor gene is downregulated in colon cancer by promoter methylation

2004 ◽  
Vol 199 (3) ◽  
pp. 92 ◽  
Author(s):  
Jimmy C. Sung ◽  
Susan McCarthy ◽  
Joel Turner ◽  
C.G. Li ◽  
Timothy J. Yeatman
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Promoter Methylation ◽  
Suppressor Gene

scholarly journals Human Mesenchymal Stem Cell Combined with a New Strontium-Enriched Bioactive Glass: An ex-vivo Model for Bone Regeneration

Materials ◽  
2019 ◽  
Vol 12 (21) ◽  
pp. 3633 ◽  
Author(s):  
Devis Bellucci ◽  
Elena Veronesi ◽  
Valentina Strusi ◽  
Tiziana Petrachi ◽  
Alba Murgia ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Ex Vivo ◽  
Human Mesenchymal Stem Cell ◽  
Cellular Model ◽  
Ex Vivo Model ◽  
Bone Differentiation ◽  
Biological Potential ◽  
Orthopedic Applications ◽  
First Time

A 3D cellular model that mimics the potential clinical application of a biomaterial is here applied for the first time to a bioactive glass, in order to assess its biological potential. A recently developed bioactive glass (BGMS10), whose composition contained strontium and magnesium, was produced in the form of granules and fully investigated in terms of biocompatibility in vitro. Apart from standard biological characterization (Simulated Body Fluid (SBF) testing and biocompatibility as per ISO10993), human bone marrow mesenchymal stromal/stem cells (BM-MSCs) were used to investigate the performance of the bioactive glass granules in an innovative 3D cellular model. The results showed that BGMS10 supported human BM-MSCs adhesion, colonization, and bone differentiation. Thus, bioactive glass granules seem to drive osteogenic differentiation and thus look particularly promising for orthopedic applications, bone tissue engineering and regenerative medicine.

NTRK3 as a novel tumor suppressor gene in colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 469-469
Author(s):  
Yanxin Luo ◽  
Andrew Kaz ◽  
Samornmas Kanngurn ◽  
William M. Grady
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Aberrant Methylation ◽  
Colon Cancer Cells ◽  
Colon Adenomas ◽  
Colon Cancer Cell Lines

469 Background: Neurotrophin tyrosine kinase receptor 3 (NTRK3) is a receptor tyrosine kinase that has been shown to be an oncogene in breast cancer and possibly in hepatocellular carcinoma. NTRK3 is a trophic dependence receptor, which is a recently described class of receptors that initiate signaling in both the ligand bound and unbound states. Through a genome-wide screen for aberrantly methylated genes, we identified aberrantly methylated NTRK3 as a frequently methylated gene in colon cancer. The aim for the present study is to determine if NTRK3 is an epigenetically silenced tumor suppressor gene in colorectal cancer. Methods: NTRK3 promoter methylation was analyzed in human colon cancer cell lines, normal colon epithelium tissue, colorectal adenomas and colorectal cancers using quantitative methylation-specific PCR and bisulfite sequencing. NTRK3 mRNA and protein expression were studied using quantitative real-time PCR, immunohistochemistry and western blotting respectively. The tumor suppressor function of NTRK3 was examined by assessing the effect of NTRK3 on cell apoptosis, cell migration and in vitro colony formation assays in colon cancer cell lines stably transfected with an NTRK3 expression construct in the presence or absence of NT-3. Results: NTRK3 is methylated in 60% of colon adenomas and in 57% of colorectal cancers. The aberrant methylation of NTRK3 suppresses NTRK3 expression and releases colon cancer cells from NTRK3 mediated apoptosis induced by the expression of NTRK3 in the absence of the ligand NT-3 via the activation of MAPK/ERK pathway. Methylation of NTRK3 also releases colon cancer cells from NTRK3 mediated suppression of motility and anchorage independent growth. The addition of NT3 to colon cancer cells transfected with NTRK3 inhibits the tumor suppressor effects of NTRK3. Conclusions: The aberrant methylation of NTRK3 is likely functionally relevant for colorectal cancer formation as NTRK3 appears to be a conditional tumor suppressor gene in the colon depending on the expression status of its ligand NT-3. NTRK3 is a novel aberrantly methylated conditional tumor suppressor gene that is frequently methylated in colon adenomas and cancers and whose discovery reveals possible novel treatment approaches to colon cancer.

Reduced expression of the metastasis suppressor gene KAI1 in advanced colon cancer and its metastases

Surgery ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 869-880 ◽  
Author(s):  
Christoph A. Maurer ◽  
Hans U. Graber ◽  
Helmut Friess ◽  
Beate Beyermann ◽  
Doris Willi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Suppressor Gene ◽  
Metastasis Suppressor ◽  
Metastasis Suppressor Gene ◽  
Advanced Colon Cancer
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