A5044224450- PI3K/AKT/mTOR signaling in cancer
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Inflammatory mediators and NSAID effects
- Histone Deacetylase Inhibitors Research
- Metabolism, Diabetes, and Cancer
- Biomarkers in Disease Mechanisms
- Cancer-related molecular mechanisms research
- Synthesis and biological activity
- Cancer Research and Treatments
- Science, Research, and Medicine
- RNA Research and Splicing
- Effects of Radiation Exposure
- Immune Response and Inflammation
- FOXO transcription factor regulation
- Cancer, Stress, Anesthesia, and Immune Response
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Signaling Pathways in Disease
- Genetics, Bioinformatics, and Biomedical Research
- Biomedical and Engineering Education
- Caveolin-1 and cellular processes
- Circular RNAs in diseases
Whitehead Institute for Biomedical Research
2020-2024
Massachusetts Institute of Technology
2024
Beth Israel Deaconess Medical Center
2015-2017
Harvard University
2015-2017
Abstract Therapy resistance and metastasis, the most fatal steps in cancer, are often triggered by a (partial) activation of epithelial–mesenchymal transition (EMT) programme. A mesenchymal phenotype predisposes to ferroptosis, cell death pathway exerted an iron oxygen-radical-mediated peroxidation phospholipids containing polyunsaturated fatty acids. We here show that various forms EMT activation, including TGFβ stimulation acquired therapy resistance, increase ferroptosis susceptibility...
Despite the high incidence of oncogenic mutations in PIK3CA, gene encoding catalytic subunit PI3K, PI3K inhibitors have yielded little clinical benefit for breast cancer patients. Recent epidemiologic studies suggested a therapeutic from aspirin intake cancers harboring PIK3CA Here, we show that mutant PIK3CA-expressing cells greater sensitivity to aspirin-mediated growth suppression than their wild-type counterparts. Aspirin decreased viability and anchorage-independent independently its...
Ferroptosis is a form of regulated cell death with roles in degenerative diseases and cancer. Excessive iron-catalyzed peroxidation membrane phospholipids, especially those containing the polyunsaturated fatty acid arachidonic (AA), central driving ferroptosis. Here, we reveal that an understudied Golgi-resident scaffold protein, MMD, promotes susceptibility to ferroptosis ovarian renal carcinoma cells ACSL4- MBOAT7-dependent manner. Mechanistically, MMD physically interacts both ACSL4...
PI3K-stimulated induction of pentraxin-3 links innate immune signaling with the growth basal-like breast cancer.
// Whitney S. Henry 1,* , David G. Hendrickson 2,3,* Francisco Beca 1 Benjamin Glass Marianne Lindahl-Allen 4 Lizhi He Zhe Ji Kevin Struhl Andrew H. Beck John L. Rinn 2,3 and Alex Toker Department of Pathology, Beth Israel Deaconess Medical Center, Harvard School, Boston, MA, USA 2 Stem Cell Regenerative Biology, University, Cambridge, 3 Broad Institute MIT Harvard, Biological Chemistry Molecular Pharmacology, * These authors have contributed equally to this work Correspondence to: Toker,...
ABSTRACT Cancer cell fate has been widely ascribed to mutational changes within protein-coding genes associated with tumor suppressors and oncogenes. In contrast, the mechanisms through which biophysical properties of membrane lipids influence cancer survival, dedifferentiation metastasis have received little scrutiny. Here, we report that cells endowed a high metastatic ability stem cell-like traits employ ether maintain low tension fluidity. Using genetic approaches lipid reconstitution...
Abstract High-grade serous ovarian cancer (HGSOC) represents the most common and lethal subtype of cancer. Despite initial response to platinum-based standard therapy, patients commonly suffer from relapse that likely originates drug-tolerant persister (DTP) cells. We generated isogenic clones treatment-naïve cisplatin-tolerant HGSOC In addition, single-cell RNA sequencing barcoded cells was performed in a xenograft model with cell lines after therapy. Published RNA-sequencing data...
Summary Ferroptosis is a form of regulated cell death with roles in degenerative diseases and cancer. driven by excessive iron-dependent peroxidation membrane phospholipids, especially those containing the polyunsaturated fatty acid arachidonic acid. Here, we reveal that an understudied Golgi scaffold protein, MMD, promotes susceptibility to ferroptosis ovarian renal carcinoma cells. Upregulation MMD correlates sensitization upon monocyte-to-macrophage differentiation. Mechanistically,...
Abstract Although aspirin is primarily administered as an antipyretic and analgesic, numerous observational randomized clinical trials have suggested a potential chemotherapeutic use. Recently, two independent studies demonstrated that use associated with superior survival in colorectal cancer patients mutant-PIK3CA but not among those the wild-type gene. Despite these seminal observations, molecular basis for this phenomenon remains poorly understood. Furthermore, whether observation occurs...
<p>Supplementary figure 1. Expression of mutant PIK3CA increases COX-2 expression and IKKbeta/NF-KB signaling.</p>
<p>Supplementary figure 2. Aspirin treatment results in activation of AMPK and decrease mTORC1 signaling.</p>
<p>Supplementary figure 1. Expression of mutant PIK3CA increases COX-2 expression and IKKbeta/NF-KB signaling.</p>
<p>Supplementary figure 2. Aspirin treatment results in activation of AMPK and decrease mTORC1 signaling.</p>
<div>Abstract<p>Despite the high incidence of oncogenic mutations in <i>PIK3CA</i>, gene encoding catalytic subunit PI3K, PI3K inhibitors have yielded little clinical benefit for breast cancer patients. Recent epidemiologic studies suggested a therapeutic from aspirin intake cancers harboring <i>PIK3CA</i>. Here, we show that mutant <i>PIK3CA</i>-expressing cells greater sensitivity to aspirin-mediated growth suppression than their wild-type...
<div>Abstract<p>Despite the high incidence of oncogenic mutations in <i>PIK3CA</i>, gene encoding catalytic subunit PI3K, PI3K inhibitors have yielded little clinical benefit for breast cancer patients. Recent epidemiologic studies suggested a therapeutic from aspirin intake cancers harboring <i>PIK3CA</i>. Here, we show that mutant <i>PIK3CA</i>-expressing cells greater sensitivity to aspirin-mediated growth suppression than their wild-type...
<p>Supplementary figure 3. Sulforhodamine assay, MCF10A cells expressing JP1520-GFP, PIK3CA-WT and PIK3CA H1047R respectively were treated with increasing concentrations of aspirin 0.5microM BYL719 for 48 hrs.</p>
<p>Supplementary figure 3. Sulforhodamine assay, MCF10A cells expressing JP1520-GFP, PIK3CA-WT and PIK3CA H1047R respectively were treated with increasing concentrations of aspirin 0.5microM BYL719 for 48 hrs.</p>
Abstract 75% of women suffering from ovarian cancer are diagnosed at late stage the disease often associated with cell infiltration into peritoneal cavity. Standard therapy is tumor resection and subsequent platin-based chemotherapy. Relapse frequently observed caused by persisting cells. Persister cells comprise a therapy-tolerant subpopulation repeated therapies presumably select for increased tolerance. The present project aims to find molecular markers identification targeted eradication...