A5083301882- Immune cells in cancer
- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- RNA modifications and cancer
- Tryptophan and brain disorders
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Hippo pathway signaling and YAP/TAZ
- Ubiquitin and proteasome pathways
- Calpain Protease Function and Regulation
- Signaling Pathways in Disease
- Cell Image Analysis Techniques
- Cancer, Hypoxia, and Metabolism
- Bipolar Disorder and Treatment
- Kruppel-like factors research
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Biochemical Acid Research Studies
- Telomeres, Telomerase, and Senescence
- Immunotherapy and Immune Responses
- Vitamin D Research Studies
- interferon and immune responses
The University of Texas Southwestern Medical Center
2016-2024
Southwestern Medical Center
2017-2024
Fred Hutch Cancer Center
2011-2015
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2010-2014
Weizmann Institute of Science
2002-2007
Transcriptional repression of E-cadherin, characteristic epithelial to mesenchymal transition, is often found also during tumor cell invasion. At metastases, migratory fibroblasts sometimes revert an phenotype, by a process involving regulation the E-cadherin–β-catenin complex. We investigated molecular basis this regulation, using human colon cancer cells with aberrantly activated β-catenin signaling. Sparse cultures mimicked invasive cells, displaying low levels E-cadherin due...
Aberrant β-catenin-TCF target gene activation plays a key role in colorectal cancer, both the initiation stage and during invasion metastasis. We identified neuronal cell adhesion molecule L1, as of signaling cancer cells. L1 expression was high sparse cultures coregulated with ADAM10, metalloprotease involved cleaving shedding L1's extracellular domain. conferred increased motility, growth low serum, transformation tumorigenesis, whereas its suppression colon cells decreased motility....
Tumors display increased uptake and processing of nutrients to fulfill the demands rapidly proliferating cancer cells. Seminal studies have shown that proto-oncogene MYC promotes metabolic reprogramming by altering glutamine metabolism in How regulates other amino acids is not fully understood. Using high-performance liquid chromatography (HPLC)-tandem mass spectrometry (LC-MS/MS), we found intracellular levels tryptophan metabolites kynurenine pathway. induced expression transporters SLC7A5...
Abstract Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated target the destruction cancer We find MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization generate metabolites in kynurenine (Kyn) pathway is reduced. Depriving through a No-Trp diet not only prevents growth but...
Evasion of apoptosis is critical in Myc-induced tumor progression. Here we report that cancer cells evade death under stress by activating calpain-mediated proteolysis Myc. This generates Myc-nick, a cytoplasmic, transcriptionally inactive cleavage product We found conversion Myc into Myc-nick cell lines and tissues derived from multiple cancers. In colon cancer, the production enhanced conditions such as hypoxia nutrient deprivation. Under these conditions, ectopic expression promotes...
Abstract Background While regulated WNT activity is required for normal development and stem cell maintenance, mutations that lead to constitutive activation of the pathway cause cellular transformation drive colorectal cancer. Activation ultimately leads nuclear translocation β-catenin which, in complex with TCF/LEF factors, promotes transcription genes necessary growth. The proto-oncogene MYC one most critical activated downstream colon Here, we investigate converse regulation by MYC....
Glioblastoma is the most common and aggressive type of cancer in brain; its poor prognosis often marked by reoccurrence due to resistance chemotherapeutic agent temozolomide, which triggered an increase expression DNA repair enzymes such as MGMT. The limited therapeutic options led studies targeted at understanding specific vulnerabilities glioblastoma cells. Metabolic adaptations leading increased synthesis nucleotides de novo biosynthesis pathways are emerging key alterations driving...
A novel phosphorylation-specific antibody (αpβ-catenin) was generated against a peptide corresponding to amino acids 33-45 of humanβ-catenin, which contained phosphorylated serines at positions 33 and 37. This is specific β-catenin reacts neither with the non-phosphorylated protein nor or plakoglobin. It weakly interacts S33Y but not S37A mutant. pβ-catenin hardly detectable in normal cultured cells accumulates (up 55% total β-catenin) upon overexpression after blocking its degradation by...
The origin of metazoans required the evolution mechanisms for maintaining differentiated cell types within a multicellular individual, in part through spatially patterns gene transcription. unicellular ancestor was presumably capable regulating expression temporally response to changing environmental conditions, and spatial differentiation may represent co-option preexisting regulatory mechanisms. Myc is critical regulator growth, proliferation, death that found all but absent other...
The MYC proto-oncogene is a transcription factor implicated in broad range of cancers. regulated by several post-translational modifications including SUMOylation, but the functional impact this modification still unclear. Here, we report that SUMO E3 ligase PIAS1 SUMOylates MYC. We demonstrate promotes, SUMOylation-dependent manner, phosphorylation at serine 62 and dephosphorylation threonine 58. These events reduce turnover, leading to increased transcriptional activity. Furthermore, find...
Significance The MYC family of transcription factors is deregulated in a broad range cancers and drives the expression genes that mediate biomass accumulation promote cell proliferation tumor initiation. We find can also trigger migration metastasis independently its transcriptional activity, via conversion to MYC-nick, truncated form localized cytoplasm. MYC-nick promotes reorganization actin cytoskeleton by inducing actin-bundling protein fascin activating Rho GTPase Cdc42, both which lead...
Neuroblastoma poses significant challenges in clinical management. Despite its relatively low incidence, this malignancy contributes disproportionately to cancer‐related childhood mortality. Tailoring treatments based on risk stratification, including MYCN oncogene amplification, remains crucial, yet high‐risk cases often confront therapeutic resistance and relapse. Here, we explore the aryl hydrocarbon receptor (AHR), a versatile transcription factor implicated diverse physiological...
MYC enhances protein synthesis by regulating genes involved in ribosome biogenesis and translation. Here, we show that MYC-induced translation is mediated the transcription factor aryl hydrocarbon receptor (AHR), which induced colonic cells. AHR promotes activating of required for translation, including OGFOD1 NOLC1. Using surface sensing (SUnSET) to measure global found silencing or its targets diminishes synthesis. Therefore, targeting downstream pathways could provide a novel approach...
Abstract A select group of patients with hepatocellular carcinomas (HCC) benefit from surgical, radiologic, and systemic therapies that include a combination anti-angiogenic immune-checkpoint inhibitors. However, because HCC is generally asymptomatic in its early stages, this not only leads to late diagnosis, but also therapy resistance. The nucleoside analogue 6-thio-dG (THIO) first-in-class telomerase-mediated telomere-targeting anticancer agent. In telomerase expressing cancer cells, THIO...
Abstract Nr-CAM, a cell-cell adhesion molecule of the immunoglobulin-like cell family, known for its function in neuronal outgrowth and guidance, was recently identified as target gene β-catenin signaling human melanoma colon carcinoma cells tissue. Retrovirally mediated transduction Nr-CAM into fibroblasts induces motility tumorigenesis. We investigated mechanisms by which can confer properties related to tumor behavior found that expression NIH3T3 protects from apoptosis absence serum...
The transcription factor AHR (aryl hydrocarbon receptor) drives the expression of genes involved in detoxification pathways cells exposed to pollutants and other small molecules. Moreover, supports transcriptional programs that promote ribosome biogenesis protein synthesis stimulated proliferate by oncoprotein MYC. Thus, is necessary for proliferation MYC-overexpressing cells. To define metabolic which cooperates with MYC supporting cell growth, here we used LC-MS-based metabolomics examine...