A5100378563- TGF-β signaling in diseases
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Genetic factors in colorectal cancer
- Cancer, Hypoxia, and Metabolism
- Colorectal Cancer Treatments and Studies
- Chronic Lymphocytic Leukemia Research
- Metabolism, Diabetes, and Cancer
- Cancer Mechanisms and Therapy
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Angiogenesis and VEGF in Cancer
- Cancer Research and Treatments
- Protease and Inhibitor Mechanisms
- Liver physiology and pathology
- Natural product bioactivities and synthesis
- Protein Degradation and Inhibitors
- DNA Repair Mechanisms
- Growth Hormone and Insulin-like Growth Factors
- Protein Kinase Regulation and GTPase Signaling
- Helicobacter pylori-related gastroenterology studies
- Protein Tyrosine Phosphatases
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Bone Metabolism and Diseases
University of Nebraska Medical Center
2008-2023
Nebraska Medical Center
2008-2023
The University of Texas MD Anderson Cancer Center
2016
Roswell Park Comprehensive Cancer Center
2004-2010
University of New Mexico
2010
Institute of Molecular and Cell Biology
2010
Biotechnology Research Institute
2002
University of Toledo
1996
Abstract FET cells, derived from an early-stage colon carcinoma, are nontumorigenic in athymic mice. Stable transfection of a dominant-negative transforming growth factor β (TGFβ) type II receptor (DNRII) into cells that express autocrine TGFβ shows loss signaling and increased tumorigenicity vivo indicating tumor suppressor activity this model. The ability tumorigenic to withstand nutrient deprivation stress (GFDS) is widely regarded as key attribute for formation progression. We...
The FET cell line, derived from an early stage colon carcinoma, is non-tumorigenic in athymic nude mice. Engineered cells that express TGF-α (FETα) display constitutively active EGFR/ErbB signaling. These readily formed xenograft tumors Importantly, FETα retained their response to TGF-beta-mediated growth inhibition, and, like the parental cells, expression of a dominant negative TGF-beta type II receptor (DNRII) (FETα/DNRII) abrogated responsiveness TGF-beta-induced inhibition and apoptosis...
Transforming growth factor β (TGFβ) type I (RI) and II (RII) receptors are essential for TGFβ signal transduction. A human colon carcinoma cell line, designated GEO, is marginally responsive to expresses a low level of RI mRNA relative cells, which highly TGFβ. Hence, the role as limiting sensitivity contribution levels malignant phenotype GEO cells were examined. Stable transfection tetracycline-regulatable rat cDNA increased TGFβ1 binding resulted in inhibition by exogenous TGFβ1. In...
Metastasis causes most deaths from cancer yet mechanistic understanding and therapeutic options remain limited. Overexpression of the phosphatase PRL-3 (phosphatase regenerating liver) is associated with metastasis colon cancer. Here, we show that a direct target signaling by TGFβ, which broadly implicated in progression metastasis. We found suppression expression TGFβ was mediated Smad-dependent inhibition transcription at level promoter activity. activation stimulated PI3K/AKT caused...
A novel series of noncovalent inhibitors cathepsin L have been designed to mimic the mode autoinhibition procathepsin L. Just like propeptide, these peptide-based a reverse-binding relative substrate and span both S' S subsites enzyme active site. In contrast previous studies in which even moderate truncation full-length propeptide led rapid reduction potency, blocked tripeptide-sized maintain nanomolar potency. Moreover, short peptides show higher selectivity (up 310-fold) for inhibiting...
In this study, we have uncovered a novel crosstalk between TGFβ and IGF-1R signaling pathways. We show for the first time that expression activation of IRS-1, an adaptor protein, is decreased by TGFβ/Smad3 signaling. Loss or attenuation leads to elevated phosphorylation IRS-1 in colon cancer cells, resulting enhanced cell proliferation, apoptosis increased tumor growth vitro vivo. Downregulation reversed Smad3 knockdown-mediated oncogenic phenotypes, indicating inhibits proliferation...
Hepatocellular carcinoma (HCC) is globally the second most common cause of cancer mortality. The majority HCC patients are diagnosed at advanced stage disease for which no curative treatments exist. TGF-β has been identified as a potential therapeutic target. However, molecular mechanisms mediating its functional switch from tumor suppressor to promoter in and interactions with other signaling pathways poorly understood. Here, we demonstrate an aberrant network between c-KIT pathway that...
Transforming growth factorβ (TGF-β) signals through Smad-dependent and Smad-independent pathways. However, Smad signaling is altered by allelic deletion or intragenic mutation of the Smad4 gene in more than half pancreatic ductal adenocarcinomas. We show here that loss Smad4-dependent leads to aberrant expression RON, a phosphotyrosine kinase receptor, RON cooperates with Smad4-independent TGF-β promote cell motility invasion. Restoring adenocarcinoma line deficient repressed expression....
Recepteur d'origine nantais (Ron) is overexpressed in a panel of pancreatic cancer cells and tissue samples from patients. Ron can be activated by its ligand macrophage stimulating protein (MSP), thereby activating oncogenic signaling pathways. Crosstalk between EGFR, c-Met, or IGF-1R may provide mechanism underlying drug resistance. Thus, targeting represent novel therapeutic strategy. IMC-RON8 the first monoclonal antibody (mAb) entering clinical trial for overexpression. Our studies show...
Background Colorectal cancer (CRC) metastasis is a leading cause of cancer-related deaths in the United States. The molecular mechanisms underlying this complex, multi-step pathway are yet to be completely elucidated. Recent reports have stressed importance intra-tumoral heterogeneity development metastatic phenotype. purpose study was characterize phenotypic between two iso-clonal human colon sublines HCT116 and HCT116b on their ability undergo colonization survive under growth factor...
Colorectal cancer (CRC) remains one of the leading causes related deaths in United States. Currently, there are limited therapeutic options for patients suffering from CRC, none which focus on cell signaling mechanisms controlled by popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent 5 (CDK5) neurodegenerative disorders. CDK5 has been implicated number cancers, most recently as an oncogene colorectal...
Fluorouracil (5-FU) remains a first-line chemotherapeutic agent for colorectal cancer. However, subset of cancer patients who have defective mismatch-repair (dMMR) pathway show resistance to 5-FU. Here, we demonstrate that the efficacy 5-FU in dMMR cells is largely dependent on DNA base excision repair (BER) pathway. Downregulation APE1, key enzyme BER pathway, decreases IC50 by 10-fold. Furthermore, discover facilitates chromatin transcription (FACT) complex via promoting recruitment and...
Microsatellite instability (MSI), which occurs in 15% of colorectal cancer, has been shown to have a lower incidence metastasis and better patient survival rates compared with microsatellite stable cancer. However, mechanistic understanding the basis for this difference is very limited. Here, we show that restoration TGFβ signaling by re-expression receptor II MSI colon cancer cells increased PI3K/AKT activation, conferred resistance growth factor deprivation stress-induced apoptosis,...
Human colon carcinoma cells HCT116 that lack transforming growth factor beta (TGF-beta) type II receptor (RII) demonstrated restoration of autocrine TGF-beta activity upon reexpression RII without restoring inhibitory responses to exogenous treatment. transfectants (designated Cl 37) had a longer lag phase relative NEO-transfected control NEO pool) before entering exponential in tissue culture. The prolonged arrest 37 was associated with markedly reduced cyclin-dependent kinase (CDK)2...
Abstract Background TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally progression malignancy. However, we present evidence here for an anti-metastatic signaling. Methods To test importance to cell survival and compared human colon carcinoma lines that are either non-tumorigenic response (FET), or tumorigenic (FETα) abrogated via introduction dominant negative TGFβRII (FETα/DN) their ability metastasize....
<div>Abstract<p>FET cells, derived from an early-stage colon carcinoma, are nontumorigenic in athymic mice. Stable transfection of a dominant-negative transforming growth factor β (TGFβ) type II receptor (DNRII) into FET cells that express autocrine TGFβ shows loss signaling and increased tumorigenicity <i>in vivo</i> indicating tumor suppressor activity this model. The ability tumorigenic to withstand nutrient deprivation stress (GFDS) is widely regarded as key...
Supplementary Figures 1-3 from Transforming Growth Factor β Induces Apoptosis through Repressing the Phosphoinositide 3-Kinase/AKT/Survivin Pathway in Colon Cancer Cells
Supplementary Figures 1-3 from Transforming Growth Factor β Induces Apoptosis through Repressing the Phosphoinositide 3-Kinase/AKT/Survivin Pathway in Colon Cancer Cells
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