A5003743625- PI3K/AKT/mTOR signaling in cancer
- Liver physiology and pathology
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Melanoma and MAPK Pathways
- Ubiquitin and proteasome pathways
- FOXO transcription factor regulation
- Hippo pathway signaling and YAP/TAZ
- Enzyme function and inhibition
- Pancreatic and Hepatic Oncology Research
- Microtubule and mitosis dynamics
- Mechanisms of cancer metastasis
- Chemical Reactions and Isotopes
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Genetics and Physical Performance
- Wnt/β-catenin signaling in development and cancer
- Mitochondrial Function and Pathology
- Kruppel-like factors research
- Immunotherapy and Immune Responses
- Cellular Mechanics and Interactions
- Cell death mechanisms and regulation
- Inflammatory mediators and NSAID effects
University of California, San Francisco
2015-2021
UCSF Helen Diller Family Comprehensive Cancer Center
2013-2021
Significance Rat sarcoma (Ras) proteins play central roles in both normal and oncogenic signaling. Mechanisms of how Ras interacts with its effectors on the cell membrane, however, are still poorly understood, significantly hampering efforts to target this molecule human cancer. Here we have used quantitative superresolution fluorescence microscopy combination carefully engineered biological systems show that dimers drive signaling through Raf-MAPK pathway. Our study suggests a new, dimer...
Defective degradation as disease mechanism Ubiquitination often targets proteins for destruction. Castel et al. describe a by which mutations in the small guanine triphosphatase RIT1 may act to cause certain developmental disorders and cancers. They detected protein, LZTR1, that interacted with wild-type but not oncogenic mutant forms of RIT1. LZTR1 acts substrate-specific adaptor ubiquitin ligase. Altered are subject ubiquitin-mediated thus accumulate. Because functions growth factor...
Abstract KRAS mutations are present in over 90% of pancreatic ductal adenocarcinomas (PDAC), and drive their poor outcomes failure to respond targeted therapies. Here we show that Leukemia Inhibitory Factor (LIF) expression is induced specifically by oncogenic PDAC LIF depletion genetic means or neutralizing antibodies prevents engraftment xenograft models. Moreover, LIF-neutralizing synergize with gemcitabine eradicate established tumors a syngeneic, Kras G12D -driven, mouse model. The...
Abstract Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with are resistant to chemotherapeutic drugs as well molecular targeting agents. Although numerous approaches ongoing find effective ways treat these tumors, there still no therapies for mutant cancer patients. Here we report that cancers more dependent on anchorage-independent culture conditions than monolayer conditions. In seeking determine mechanisms contribute...
Significance Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and one deadly types, with a 5-y survival rate below 10%. One reason for this high mortality that PDAC cells have an enhanced ability to survive proliferate despite existing in nutrient-deprived environments. Understanding metabolic rewiring enables nutrient scavenging rapid processing can provide new strategies develop effective treatment options intractable disease. In study, convergent...
Abstract Spred proteins negatively regulate Ras/MAPK signaling following growth factor stimulation. Inhibition of Ras primary occurs through Spreds ability to bind and localize NF1, a RasGAP major tumor suppressor, the plasma membrane. Spred1 NF1 loss-of-function mutations occur across multiple cancer types including non-small cell lung carcinoma, glioblastoma, melanoma, stomach uterine carcinosarcoma. Here we demonstrate that EGFR disrupts Spred1-NF1 binding. Mass spectrometry was performed...
Abstract UDP-glucose pyrophosphorylase 2 (UGP2) is a lynchpin metabolic enzyme that rests at the convergence of multiple pathways regulating both glycogen synthesis and glycosylation modifications. Here we elucidated essential role UGP2-mediated in maintenance KRAS-driven cancer using vitro vivo models. A key effector KRAS oncogenic function transcription factor YAP. We identified YAP/TEAD complex as major regulator UGP2 mRNA expression enzymatic activity genomic perturbations, correlative...
Abstract Spred proteins negatively regulate Ras/MAPK signaling following mitogen stimulation. Inhibition of Ras primary occurs through Spreds ability to bind and localize NF1, a RasGAP major tumor suppressor, the plasma membrane. Loss-of-function Spred1 NF1 mutations occur across multiple cancer types including melanoma, non-small cell lung carcinoma, stomach uterine carcinosarcoma. Here we demonstrate that oncogenic EGFR disrupts Spred1-NF1 binding. Mass spectrometry was performed on cells...
Abstract Cancer stem cells (CSCs) can cause cancer treatment failures and tumor recurrence due to their cell-like properties, such as the unlimited self-renewal, tumorigenicity, chemo-resistance. Ras is most common oncogene in human cancers, but its roles properties have not been convincingly demonstrated. With a high degree of sequence homology well sets downstream effectors upstream affecters, three isoforms Ras, N-, H- K-Ras, long assumed be functionally redundant. However, knockout N- or...
<p>supplementary figure 6. Anchorage independent culture conditions enhance Met translation.</p>
<div>Abstract<p>Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with are resistant to chemotherapeutic drugs as well molecular targeting agents. Although numerous approaches ongoing find effective ways treat these tumors, there still no therapies for mutant cancer patients. Here we report that cancers more dependent on anchorage-independent culture conditions than monolayer conditions. In seeking determine...
<p>supplementary figure 5. Activation of Met signaling rescues K-Ras knock down-mediated growth suppression.</p>
<p>supplementary figure 4. Sensitivity to MEK1/2 inhibitor (GSK1120212) in monolayer and anchorage independent culture conditions.</p>
<p>supplementary figure 3. HGF, but not EGF, plays an essential role in proliferation of cells anchorage independent culture conditions.</p>
<p>supplementary figure 2. K-Ras is required for anchorage independent growth in a broad panel of mutant cells.</p>
<div>Abstract<p>Oncogenic K-Ras mutation occurs frequently in several types of cancers, including pancreatic and lung cancers. Tumors with are resistant to chemotherapeutic drugs as well molecular targeting agents. Although numerous approaches ongoing find effective ways treat these tumors, there still no therapies for mutant cancer patients. Here we report that cancers more dependent on anchorage-independent culture conditions than monolayer conditions. In seeking determine...
<p>supplementary figure 1. Dependence of K-Ras mutant cells on in monolayer and anchorage independent culture conditions.</p>
<p>supplementary figure 5. Activation of Met signaling rescues K-Ras knock down-mediated growth suppression.</p>
<p>supplementary figure 2. K-Ras is required for anchorage independent growth in a broad panel of mutant cells.</p>
<p>supplementary figure 6. Anchorage independent culture conditions enhance Met translation.</p>
<p>Supplemtal figure legends 1-5</p>
<p>Supplemtal figure legends 1-5</p>