Publication

CL9/9L-beta-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer

Michel Aguet, Patrick Rodriguez, Mauro Delorenzi, Norbert Wiedemann, Pascale Anderle Pedone, Andreas Eduard Moor, Sylvie André Baflast, Frédérique Baruthio
2015
Journal Articles

Abstract

BCL9/9L proteins enhance the transcriptional output of the beta-catenin/TCF transcriptional complex and contribute critically to upholding the high WNT signaling level required for stemness maintenance in the intestinal epithelium. Here we show that a BCL9/9L-dependent gene signature derived from independent mouse colorectal cancer (CRC) models unprecedentedly separates patient subgroups with regard to progression free and overall survival. We found that this effect was by and large attributable to stemness related gene sets. Remarkably, this signature proved associated with recently described poor prognosis CRC subtypes exhibiting high stemness and/or epithelial-to-mesenchymal transition (EMT) traits. Consistentwith the notion that high WNT signaling is required for stemnessmaintenance, ablating Bcl9/9l-beta-catenin inmurine oncogenic intestinal organoids provoked their differentiation and completely abrogated their tumorigenicity, while not affecting their proliferation. Therapeutic strategies aimed at targetingWNT responses may be limited by intestinal toxicity. Our findings suggest that attenuating WNT signaling to an extent that affects stemness maintenance without disturbing intestinal renewal might be well tolerated and prove sufficient to reduce CRC recurrence and dramatically improve disease outcome. (C) 2015 The Authors. Published by Elsevier B.V.

Official source

https://infoscience.epfl.ch/entities/publication/3021d006-e0f1-44e5-abd2-76ebc275238c

Michel Aguet, Patrick Rodriguez, Mauro Delorenzi, Norbert Wiedemann, Pascale Anderle Pedone, Andreas Eduard Moor, Sylvie André Baflast, Frédérique Baruthio
2015
Journal Articles

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/3021d006-e0f1-44e5-abd2-76ebc275238c

Related concepts (29)

Wnt signaling pathway

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

Autocrine signaling

Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with paracrine signaling, intracrine signaling, or classical endocrine signaling. An example of an autocrine agent is the cytokine interleukin-1 in monocytes. When interleukin-1 is produced in response to external stimuli, it can bind to cell-surface receptors on the same cell that produced it.

Colorectal cancer

Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and fatigue. Most colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying genetic disorders. Risk factors include diet, obesity, smoking, and lack of physical activity.

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