A5068008988- Cancer-related Molecular Pathways
- Pluripotent Stem Cells Research
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cancer Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Chemokine receptors and signaling
- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Cancer, Hypoxia, and Metabolism
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- Cytokine Signaling Pathways and Interactions
- Synthesis and Characterization of Heterocyclic Compounds
- MicroRNA in disease regulation
- interferon and immune responses
- Metabolism, Diabetes, and Cancer
- Cancer-related gene regulation
- Computational Drug Discovery Methods
- Science, Research, and Medicine
- Cancer, Lipids, and Metabolism
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Microtubule and mitosis dynamics
Memorial Sloan Kettering Cancer Center
2021-2024
Kettering University
2022-2023
Weizmann Institute of Science
2008-2018
Tel Aviv University
2010
Johns Hopkins University
2010
Georgetown University
1995
The tumor suppressor p53 is frequently mutated in human cancer. Common mutant (mutp53) isoforms can actively promote cancer through gain-of-function (GOF) mechanisms. We report that mutp53 prolongs TNF-α-induced NF-κB activation cultured cells and intestinal organoid cultures. Remarkably, when exposed to dextran sulfate sodium, mice harboring a germline mutation develop severe chronic inflammation persistent tissue damage, are highly prone inflammation-associated colon This GOF manifested by...
Emerging notion in carcinogenesis ascribes tumor initiation and aggressiveness to cancer stem cells (CSCs). Specifically, colorectal (CRC) development was shown be compatible with CSCs hypothesis. Mutations p53 are highly frequent CRC, known facilitate aggressiveness. Yet, the link between mutant is not well-established. In present study, we set examine whether oncogenic proteins may augment phenotype. By genetic manipulation of several cellular systems, demonstrated that enhances...
Uncontrolled accumulation of reactive oxygen species (ROS) causes oxidative stress and induces harmful effects. Both high ROS levels p53 mutations are frequent in human cancer. Mutant forms known to actively promote malignant growth. However, no mechanistic details about the contribution mutant excessive cancer cells. Herein we examined effect p53R273H, a commonly occurring mutated form, on expression phase 2 detoxifying enzymes, ability cells readopt reducing environment after exposure...
Significance Mutations of p53 occur in approximately 50% human cancer. missense mutations exhibit gain-of-function activities. In this study, we discovered a previously unidentified mechanism mutant osteosarcoma and mammary tumors. Our data indicate that binds to E26 transformation-specific motifs the Pla2g16 phospholipase promoter induce its expression, which leads more aggressive metastatic phenotypes. Thus, study implicates regulation lipid metabolism cancer cells confer gain-of-function....
It is well accepted that tumor microenvironment essential for cells survival, cancer progression and metastasis. However, the mechanisms by which interact with their surrounding at early stages of development are largely unidentified. The aim this study was to identify specific molecules involved in stromal–epithelial interactions might contribute prostate formation. Here, we show conditioned medium (CM) from immortalized non-transformed epithelial stimulated stromal express cancer-related...
Fibroblasts located adjacent to the tumor [cancer-associated fibroblasts (CAFs)] that constitute a large proportion of cancer-associated stroma facilitate transformation process. In this study, we compared biological behavior CAFs were isolated from prostate their normal-associated fibroblast (NAF) counterparts. formed more colonies when seeded at low cell density, exhibited higher proliferation rate and less prone contact inhibition. contrast general notion high levels α-smooth muscle actin...
Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that amplification may play a causal role tumorigenesis. According to an alternative view, imbalance is mainly common side effect cancer progression. To test whether specific genomic aberration might serve as initiating event, we established vitro system models the evolutionary process early stages prostate tumor formation; normal cells were immortalized...
Abstract In this study, we focus on the analysis of a previously identified cancer-related gene signature (CGS) that underlies cross talk between p53 tumor suppressor and Ras oncogene. CGS consists large number known downstream target genes were synergistically upregulated by wild-type loss oncogenic H-RasG12V expression. Here show expression strongly correlates with malignancy. an attempt to elucidate molecular mechanisms underling cooperation H-RasG12V, distinguished pathways may account...
Concomitant expression of mutant p53 and oncogenic Ras, leading to cellular transformation, is well documented. However, the mechanisms by which various categories cooperate with Ras remain largely obscure. In this study we suggest that different H-Ras in manners induce a unique pattern cancer related gene signature (CGS). The DNA-contact mutants (p53R248Q p53R273H) exhibited highest level CGS cooperating NFκB. Furthermore, Zn+2 region conformational (p53R175H p53H179R) induced elevating...
Insulin resistance is a condition associated with obesity, type 2 diabetes(T2D), hyperinsulinemia, hyperglycemia and defined by reduced sensitivity to insulin signaling. Molecular causes early signaling events underlying are not well understood. Here we show that activation of PI3K/AKT/mTOR in target tissues, mTORC1 induction PTEN translation, negative regulator PI3K We hypothesized due dependent prevents further increases In diet induced animal model obesity resistance, levels increased...
Partial gain of chromosome arm 17q is an abundant aberrancy in various cancer types such as lung and prostate with a prominent occurrence prognostic significance neuroblastoma – one the most common embryonic tumors. The specific genetic element/s responsible for cancer-promoting effect these aberrancies yet to be defined although many genes located have been proposed play role malignancy. We report here characterization naturally-occurring, non-reciprocal translocation der(X)t(X;17) human...
Compelling evidences have rendered the tumor microenvironment a crucial determinant in cancer outcome. Activating transcription factor 3 (ATF3), stress response factor, is known to dichotomous role cells, acting either as suppressor or an oncogene context-dependent manner. However, its expression and possible are hitherto unknown. Here we show that ATF3 upregulated stromal compartment of several types cancer. Accordingly, Cancer-associated fibroblasts (CAFs) ectopically expressing...
Mutations in the p53 tumor suppressor protein are highly frequent tumors and often endow cells with tumorigenic capacities. We sought to examine a possible role for mutant cross-talk between cancer their surrounding stroma, which is crucial factor affecting outcome. Here we present novel model enables individual monitoring of response stromal (fibroblasts) co-culturing. found that fibroblasts elicit interferon beta (IFNβ) pathway when contact cells, thereby inhibiting migration. Mutant was...
It is well accepted that malignant transformation associated with unique metabolism. Malignant involves a variety of cellular pathways are initiation and progression the process remain to be deciphered still. Here we used mouse model mutant p53 presents stepwise progressive adult Mesenchymal Stem Cells (MSCs). While established parental p53Mut-MSCs induce tumors, p53WT-MSCs were in parallel, did not. Furthermore, tumor lines derived from (p53Mut-MSC-TLs), exhibited yet more aggressive...
Mutations in the tumor suppressor p53 are most frequent alterations human cancer. These mutations include p53-inactivating as well oncogenic gain-of-function (GOF) that endow with capabilities to promote progression. A primary challenge cancer therapy is targeting stemness features and stem cells (CSC) account for initiation, metastasis, relapse. Here we show vitro cultivation of tumors derived from mutant murine bone marrow mesenchymal (MSC) gives rise aggressive lines (TL). MSC-TLs...