Showing papers in "Cancer Cell in 2012"

TL;DR: Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types, which presents interesting new targets for anticancer therapy.

TL;DR: It is argued that altered metabolism has attained the status of a core hallmark of cancer.

TL;DR: It is shown that systemic administration of an enzymatic agent can ablate stromal HA from autochthonous murine PDA, normalize IFP, and re-expand the microvasculature and in combination with the standard chemotherapeutic, gemcitabine, the treatment permanently remodels the tumor microenvironment and consistently achieves objective tumor responses, resulting in a near doubling of overall survival.

TL;DR: It is demonstrated that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup.

TL;DR: It is shown that Nrf2 redirects glucose and glutamine into anabolic pathways, especially under the sustained activation of PI3K-Akt signaling, which enables NRF2 to promote metabolic activities that support cell proliferation in addition to enhancing cytoprotection.

TL;DR: It remains uncertain whether the stem cell model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells.

TL;DR: Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.

TL;DR: A recent outcome of whole exome sequencing of thousands of human cancers has been the unexpected discovery of many inactivating mutations in genes that control the epigenome, which contributes to cancer.

TL;DR: In vivo, the requirement of "reversible EMT" in tumor metastasis is demonstrated and may resolve the controversy on the importance of EMT in carcinoma metastasis.

TL;DR: A prometastatic program induced by TGF-β in the microenvironment that associates with a high risk of CRC relapse upon treatment is unveiled and could be exploited to improve the diagnosis and treatment of CRC.

TL;DR: It is shown that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties, and is a biomarker associated with patient survival and lack of metastasis.

TL;DR: It is shown that tumor-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) is necessary and sufficient to drive the development of Gr-1(+) CD11b(+) cells that suppressed antigen-specific T cells in pancreatic ductal adenocarcinoma.

TL;DR: A repair-independent requirement for FA genes, including FANCD2, and BRCA1 in protecting stalled replication forks from degradation is shown, implying a unified molecular mechanism for repair- independent functions of FA, RAD51, and PSA1/2 proteins in preventing genomic instability and suppressing tumorigenesis.

TL;DR: Several genetic alterations that activate kinase signaling in Ph-like ALL induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.

TL;DR: An oncogenic Kras(G12D)-dependent upregulation of GM-CSF in mouse pancreatic ductal epithelial cells (PDECs) is demonstrated and a pathway that linksoncogenic activation to the evasion of antitumor immunity is identified.

TL;DR: It is shown that transient exposure of cultured and primary leukemic and epithelial tumor cells to clinically relevant nanomolar doses produce an antitumor "memory" response, including inhibition of subpopulations of cancer stem-like cells.

TL;DR: It is suggested that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features, and formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9.

TL;DR: It is identified that ASXL1 mutations result in loss of polycomb repressive complex 2 (PRC2)-mediated histone H3 lysine 27 (H3K27) tri-methylation, and that loss of AS XL1 in vivo collaborates with NRASG12D to promote myeloid leukemogenesis.

TL;DR: The data establish KDM1A as a key effector of the differentiation block in MLL leukemia, which may be selectively targeted to therapeutic effect, and drugs active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations are established.

TL;DR: It is demonstrated that vascular endothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhanced recruitment of the protein tyrosine phosphatase 1B to a MET/VEGFR2 heterocomplex, thereby suppressing HGF-dependent MET phosphorylation and tumor cell migration.

TL;DR: It is shown that rDNA transcription can be therapeutically targeted with the small molecule CX-5461 to selectively kill B-lymphoma cells in vivo while maintaining a viable wild-type B cell population.

TL;DR: It is shown that P5091 is an inhibitor of deubiquitylating enzyme USP7, which induces apoptosis in MM cells resistant to conventional and bortezomib therapies, which supports clinical evaluation of USP 7 inhibitor, alone or in combination, as a potential MM therapy.

TL;DR: BRAF(V600E) drives tumors by dysregulating ERK signaling, and its activation is Ras independent and it signals as a RAF-inhibitor-sensitive monomer, and combined inhibition results in enhancement of ERK pathway inhibition and antitumor activity.

TL;DR: Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies.

TL;DR: It is suggested that HBV infection and activity of the TGF-β-miR-34a-CCL22 axis serve as potent etiological factors to predispose HCC patients for the development of PVTT, possibly through the creation of an immune-subversive microenvironment to favor colonization of disseminated HCC cells in the portal venous system.

TL;DR: It is shown that oncogenic KRAS upregulates endogenous EGFR expression and activation, the latter being dependent on the EGFR ligand sheddase, ADAM17, which effectively eliminates KRAS-driven tumorigenesis in vivo.

TL;DR: In this paper, pericyte depletion was associated with increased hypoxia, epithelial-to-mesenchymal transition (EMT), and Met receptor activation in breast cancer patients.

TL;DR: The mechanism by which IKK2/β/NF-κB is activated by Kras(G12D) through dual feedforward loops of IL-1α/p62 is demonstrated, demonstrating a mechanistic link between IKK 2/β and Kras (G 12D) in PDAC inception.

TL;DR: Live imaging of chemotherapy-treated mouse mammary carcinomas allowed us to follow drug distribution, cell death, and tumor-stroma interactions, and associations between vascular leakage and response to doxorubicin, showing that the microenvironment contributes critically to drug response via regulation of vascular permeability and innate immune cell infiltration.

TL;DR: OxPhos-DLBCL subset, which harbors the signature of genes involved in mitochondrial metabolism, is insensitive to inhibition of BCR survival signaling but is functionally undefined.