scholarly journals Erratum: Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Marco Gerling ◽  
Nikè V.J.A. Büller ◽  
Leonard M Kirn ◽  
Simon Joost ◽  
Oliver Frings ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumour Growth ◽  
Hedgehog Signalling

scholarly journals Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Marco Gerling ◽  
Nikè V. J. A. Büller ◽  
Leonard M. Kirn ◽  
Simon Joost ◽  
Oliver Frings ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Colon Cancer ◽  
Stem Cell ◽  
Tumour Growth ◽  
Hedgehog Signalling ◽  
Reporter Mice ◽  
Tumour Load ◽  
Colonic Tumour ◽  
Bmp Signalling

Abstract A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of colitis-associated colon cancer, and that downstream Hh signalling is restricted to the stroma. Functionally, stroma-specific Hh activation in mice markedly reduces the tumour load and blocks progression of advanced neoplasms, partly via the modulation of BMP signalling and restriction of the colonic stem cell signature. By contrast, attenuated Hh signalling accelerates colonic tumourigenesis. In human CRC, downstream Hh activity is similarly reduced and canonical Hh signalling remains predominantly paracrine. Our results suggest that diminished downstream Hh signalling enhances CRC development, and that stromal Hh activation can act as a colonic tumour suppressor.

scholarly journals Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323363
Author(s):  
Ester Pagano ◽  
Joshua E Elias ◽  
Georg Schneditz ◽  
Svetlana Saveljeva ◽  
Lorraine M Holland ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumour Growth ◽  
Tumour Microenvironment ◽  
Tube Formation ◽  
Tissue Remodelling ◽  
Colon Cancers ◽  
Inflammatory Bowel ◽  
Ion Pumping ◽  
G Protein Coupled

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.

scholarly journals Selective Wnt/β-catenin small-molecule inhibitor CWP232228 impairs tumour growth of colon cancer

2019 ◽  
Vol 30 ◽  
pp. v243 ◽  
Author(s):  
J.Y. Kim ◽  
K.K. Lee ◽  
E.H. Jung ◽  
E. Ha ◽  
M. Krishnan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Small Molecule ◽  
Tumour Growth ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor

Su1732 Colon Cancer Stem Cell Proliferation and Tumour Growth Are Promoted by Nitric Oxide Synthase-2

2013 ◽  
Vol 144 (5) ◽  
pp. S-463
Author(s):  
Maria Ausiliatrice Puglisi ◽  
Valentina Tesori ◽  
Achille Cittadini ◽  
Giovanni Gasbarrini ◽  
Giovambattista Pani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Tumour Growth ◽  
Stem Cell Proliferation ◽  
Colon Cancer Stem Cell ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

scholarly journals Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance

2014 ◽  
Vol 9 (1) ◽  
pp. 167-178 ◽  
Author(s):  
Maryam A. Hamdollah Zadeh ◽  
Elianna M. Amin ◽  
Coralie Hoareau-Aveilla ◽  
Enric Domingo ◽  
Kirsty E. Symonds ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Alternative Splicing ◽  
Tumour Growth ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Isoform Expression
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