RSPO3 expands intestinal stem cell and niche compartments and drives tumorigenesis

Conclusions We provide in vivo evidence that RSPO3 stimulates the crypt stem cell and niche compartments and drives rapid intestinal tumorigenesis. This establishes RSPO3 as a potent driver of intestinal cancer and proposes RSPO3 as a candidate target for therapy in patients with colorectal cancer harbouring RSPO3 fusions.
Source: Gut - Category: Gastroenterology Authors: Tags: Open access GI cancer Source Type: research

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In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Cosmeri Rizzato1, Javier Torres2, Elena Kasamatsu3, Margarita Camorlinga-Ponce2, Maria Mercedes Bravo4, Federico Canzian5 and Ikuko Kato6* 1Department of Translation Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy 2Unidad de Investigación en Enfermedades Infecciosas, Unidades Médicas de Alta Especialidad Pediatría, Instituto Mexicano del Seguro Social, Mexico City, Mexico 3Instituto de Investigaciones en Ciencias de la Salud, National University of Asunción, Asunción, Paraguay 4Grupo de Investigación en Biología del C&aacut...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
This study was carried out in accordance with the recommendations of the Case Western Reserve University IACUC committee. The protocol was approved by the Case Western Reserve University IACUC committee. Author Contributions LRD and DW helped design research studies, analyze data and write the manuscript. ZL, RL, and ND conducted experiments, acquired and analyzed data, and assisted with manuscript preparation. LDM conducted experiments and analyzed data. FC assisted with research design. Funding This work was supported by the NIH P30CA043703, K1CA113838, and R01DK081395. Conflict of Interest Statement The authors de...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions The current review reports recent epidemiological and experimental data supporting the bright future of dietary polyphenols as chemopreventive, anti-inflammatory, immunomodulatory, and anticancer agents in CRC (Figure 1). The polyphenol-rich diet not only may represent a chemopreventive treatment but also has important function on immune system by promoting symbiont and commensal bacterial populations, increases reciprocal interaction between host and microbiota which in turn have important effects on immune function Evidence underlines the use of polyphenols as sensitizers of chemo/radiotherapies paving the w...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions As the intestinal mucosa surface constitutes the major surface of the body which is in direct contact with the outer environment, intestinal immune homeostasis must be accurately regulated. The interplay between commensal microbiota, intestinal stromal cells, and the mucosal immune system components should guarantee the intestinal homeostasis to avoid a sustained inflammation that could induce tissue damage. However, several factors can lead to inflammation through homeostasis breakdown. Figure 1 summarizes the main points that have been reviewed here. We have described what it is known so far about the role o...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study was provided by the Canadian Institutes of Health Research and the Manitoba Health Research Council. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References 1. Sprent J, Kishimoto H. The thymus and central tolerance. Philos Trans R Soc Lond B Biol Sci. (2001) 356:609–16. doi: 10.1098/rstb.2001.0846 PubMed Abstract | CrossRef Full Text | Google Scholar 2. Sakaguchi S, Wing K, Miyara M. Regulatory T cells - a brief history and perspective. ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancer (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiological Wnt activity, we have performed transcriptome and proteome profiling in isogenic human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9-induced APC loss. We could catalog two nonoverlapping molecular signatures that were stable at distinct lev...
Source: The Journal of Experimental Medicine - Category: Internal Medicine Authors: Tags: Solid Tumors, Stem Cells & Regeneration, Human Disease Genetics Articles Source Type: research
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