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The serrated neoplasia pathway gives rise to a distinct subgroup of colorectal cancers distinguished by the presence of mutant BRAF and the CpG Island Methylator Phenotype (CIMP). BRAF mutant CRC are commonly associated with microsatellite instability, which have an excellent clinical outcome. However, a proportion of BRAF mutant CRC retain microsatellite stability and have a dismal prognosis. The molecular drivers responsible for the development of this cancer subgroup are unknown. To address this, we established a murine model of BRAF mutant microsatellite stable CRC and comprehensively investigated the exome and transcriptome to identify molecular alterations in signaling pathways that drive malignancy. Exome sequencing of murine serrated lesions (mSL) and carcinomas identified frequent hot spot mutations within the gene encoding β-catenin (Ctnnb1). Immunohistochemical staining of β-catenin indicated that these mutations led to an increase in the presence of aberrant nuclear β-catenin that resulted in gene expression changes in targets of β-catenin transcription. Gene expression profiling identified a significant enrichment for transforming growth factor-β (TGF-β) signaling that was present in mSL and carcinomas. Early activation of TGF-β suggests that this pathway may be an early cue directing mSL to microsatellite stable carcinoma. These findings in the mouse model support the importance of alterations in WNT and TGF-β signaling during the transition of human sessile serrated lesions to malignancy.
This article was published in the following journal.
Name: Neoplasia (New York, N.Y.)
Nrf2 constitutes a therapeutic reference point for renal fibrosis and chronic kidney diseases. Nrf2-related signaling pathways are recognized to temper endothelial-to-mesenchymal transition (EMT) in f...
In angiosperms, floral transition is a key developmental transition from the vegetative to reproductive growth, and requires precise regulation to maximize the reproductive success. A complex regulato...
Girls with Turner Syndrome with Y-chromosome material (TS+Y) are assumed to have non-functional gonads with increased tumor risk, therefore prophylactic gonadectomy is recommended at diagnosis. This s...
The aim of the present study was to investigate and compare the effects of acute and chronic (21-day) administration of agonist (WAY-181187) and antagonist (SB-742457) of the 5-hydroxytryptamine 6 rec...
Cancer cell biology takes the advantage of identifying diverse cellular signaling pathways that are disrupted in cancer. Signaling pathways are an important means of communication from exterior of cel...
Purpose: To develop a screening metric by examining both the characteristics of the preoperative tear film and the intracellular signaling pathways of conjunctival goblet cells in order t...
The purpose of the study is to determine apoptotic signaling pathways such as Survivin, Bcl-2, Bax, c-Myc and caspase-9 expression levels in rats model with iatrogenic endometrial hyperpla...
The link between the products of synthetic chemistry and cancer is at the heart of much research. Recent work has identified the use of plant protection agents by farmers as a risk factor ...
This pilot study seeks to evaluate the feasibility of measuring the proximal effects of concurrent chemoradiotherapy (CRT) on the expression of potential therapeutic target molecules in He...
Squamous Cell Carcinoma (SCC) is one of the most common malignancies in caucasian population. The effect of the immune system on the development of skin tumors has been demonstrated in tra...
A sub-family of smad proteins that inhibit cell signaling by RECEPTOR-REGULATED SMAD PROTEINS. They form autoinhibitory feedback loops in the TGF-BETA signaling pathway and mediate signaling cross-talk with other signaling pathways
A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the CELL CYCLE, membrane trafficking, and RNA processing. In DROSOPHILA casein kinase Ialpha has been in regulation of Hedghog and Wingless signaling pathways. Multiple isoforms of casein kinase Ialpha exist and are due ALTERNATIVE SPLICING.
An SHC-signaling adaptor protein that links GROWTH FACTOR RECEPTORS to SIGNAL TRANSDUCTION PATHWAYS in neurons, including NEUROTROPHINS signaling in the CENTRAL NERVOUS SYSTEM.
Phosphoinositide phosphatases that catalyze the removal of the 5' phosphate from INOSITOL 1,4,5-TRISPHOSPHATE or myo-inositol 1,3,4,5-tetrakisphosphate, resulting in inositol 1,4-bisphosphate and phosphate. They have important functions in the metabolism of INOSITOL PHOSPHATES and inositol 1,4,5-trisphosphate signaling pathways such as CALCIUM SIGNALING.
A glycogen synthase kinase-3 type enzyme that functions in ENERGY METABOLISM; EMBRYONIC DEVELOPMENT; and NEUROGENESIS. It is also involved in PROTEIN BIOSYNTHESIS and regulates cell growth and proliferation as a component of the WNT SIGNALING PATHWAY and other signaling pathways. Certain polymorphisms in the GSK3B gene have been associated with PARKINSON DISEASE; ALZHEIMER DISEASE; and BIPOLAR DISORDER.
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Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...