Showing papers in "Cancer Cell in 2013"

TL;DR: The biological significance and clinical implications of these findings are discussed, with an emphasis on novel approaches that effectively target TAMs to increase the efficacy of such therapies.

TL;DR: It is shown that patient-derived glioma sphere cultures that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics, and it is suggested that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process.

TL;DR: It is demonstrated that neoadjuvant local low-dose gamma irradiation (LDI) causes normalization of aberrant vasculature and efficient recruitment of tumor-specific T cells in human pancreatic carcinomas and T-cell-mediated tumor rejection and prolonged survival in otherwise immune refractory spontaneous and xenotransplant mouse tumor models.

TL;DR: GC B cell (GCB)-type diffuse large B cell lymphomas (DLBCLs) are mostly addicted to EZH2 but not the more differentiated activated B cell(ABC)-type DLBCLS, thus clarifying the therapeutic scope of EZh2 targeting.

TL;DR: It is demonstrated that trabectedin, a recently approved chemotherapeutic agent, induces rapid apoptosis exclusively in mononuclear phagocytes, and this unexpected property may be exploited in different therapeutic strategies.

TL;DR: It is shown that BRAF inhibition also induces an oxidative phosphorylation gene program, mitochondrial biogenesis, and the increased expression of the mitochondrial master regulator, PGC1α, and a target of BRAF, the melanocyte lineage factor MITF, directly regulates the expression of P GC1α.

TL;DR: It is shown that HK2 is required for tumor initiation and maintenance in mouse models of KRas-driven lung cancer, and ErbB2-driven breast cancer, despite continued HK1 expression, and systemic Hk2 deletion is therapeutic in mice bearing lung tumors without adverse physiological consequences.

TL;DR: Functional study of genes marked by super-enhancers identifies DLBCLs dependent on OCA-B and suggests a strategy for discovering unrecognized cancer dependencies.

TL;DR: It is shown that EZH2 binds to and methylates STAT3, leading to enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3.

TL;DR: This study indicates that the loss of FBP1 is a critical oncogenic event in EMT and BLBC.

TL;DR: Methylome analysis of a large paraganglioma cohort identified three stable clusters, associated with distinct clinical features and mutational status, and inactivating FH mutations were identified in the only hypermethylated tumor without SDHx mutations.

TL;DR: It is shown that reduced H3K27me3 levels and DNA hypomethylation act in concert to activate gene expression in K27M mutant pHGGs, and it is demonstrated that this is caused by aberrant recruitment of the PRC2 complex to K 27M mutant H3.3.

TL;DR: It is reported that the oncogenic melanocyte lineage-specification transcription factor MITF drives PGC1α (PPARGC1A) overexpression in a subset of human melanomas and derived cell lines.

TL;DR: These findings support a two-tiered approach combining anticancer agents that eliminate rapidly proliferating melanoma cells with inhibitors of the drug-resistant slow-cycling subpopulation, and support an intrinsic multidrug resistance based on the survival of a tumor cell subpopulation.

TL;DR: Phenformin is suggested as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors, resulting in prolonged survival in these tumors.

TL;DR: It is reported that hypoxia-induced Semaphorin 3A (Sema3A) acts as an attractant for TAMs by triggering vascular endothelial growth factor receptor 1 phosphorylation through the associated holoreceptor, composed of Neuropilin-1 (Nrp1) and PlexinA1/PlexinA4.

TL;DR: The prodrug FTY720 decreased SphK1 and S1PR1 expression and eliminated the NF-κB/IL-6/STAT3 amplification cascade and development of CAC, even in Sphk2(-/-) mice, and may be useful in treating colon cancer in individuals with ulcerative colitis.

TL;DR: This study demonstrates that high-grade serous tumors can originate in fallopian tubal secretory epithelial cells and establishes serous tubal intraepithelial carcinoma as the precursor lesion to high- grade serous ovarian and peritoneal carcinomas in animal models targeting the Brca, Tp53, and Pten genes.

TL;DR: How cancer cells acquire the competence to colonize distant organs remains a central question in cancer biology and experimental work and high-resolution sequencing of human tissues have started to reveal the molecular and tumor evolutionary principles that underlie the emergence of metastatic traits.

TL;DR: It is shown that adenine nucleotides released from tumor cell-activated platelets induce opening of the endothelial barrier to allow transendothelial migration of tumor cells and thereby promote cancer cell extravasation.

TL;DR: A functional metabolic portrait of 46 independently derived breast cell lines is constructed, revealing a therapeutic target in breast tumors of poorest prognosis and a lead compound for rapid, effective drug development.

TL;DR: It is found that regulation and functions of EMT-TFs are different in malignant melanoma and this switch results in E-cadherin loss, enhanced invasion, and constitutes an independent factor of poor prognosis in melanoma patients.

TL;DR: This work identifies Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 for gene repression.

TL;DR: It is shown that, without direct cell-cell contact, ECs secrete factors that promoted the CSC phenotype in CRC cells via Notch activation, and ECs play an active role in promoting Notch signaling and the C SC phenotype by secreting soluble Jagged-1.

TL;DR: Findings are discussed in the context of results obtained from the clinical analyses of CTCs and DTCs, which demonstrate that the animal models mimic, in many aspects, the complex situation in patients.

TL;DR: It is reported that mutp53 prolongs TNF-α-induced NF-κB activation in cultured cells and intestinal organoid cultures, and might explain the early appearance of p53 mutations in human CAC.

TL;DR: The data uncover SIRT4 as an important component of the DNA damage response pathway that orchestrates a metabolic block in glutamine metabolism, cell cycle arrest, and tumor suppression.

TL;DR: Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in serous ovarian cancer (OvCa) and predicted eight key miRNAs were predicted to regulate 89% of the targets in this network.

TL;DR: Genetic evidence is presented that loss of CXCR2 dramatically suppresses chronic colonic inflammation and colitis-associated tumorigenesis through inhibiting infiltration of myeloid-derived suppressor cells (MDSCs) into colonic mucosa and tumors in a mouse model of colitis -associated cancer.

TL;DR: A 16 gene signature that outperformed a larger in-vitro-derived signature in clinical data sets is identified, showing the importance of persistent AR signaling in CRPC.