Menée in vivo, cette étude met en évidence divers mécanismes par lesquels la mutation P81S du gène VHL favorise la croissance d'un carcinome rénal à cellules claires associé à une exposition professionelle au trichloroéthylène

New Insights into von Hippel-Lindau Function Highlighted by Investigation of the Trichloroethylene-Induced p.P81S Hotspot Mutation

Neckers, Len ; Ricketts, Christopher J. ; Marston Linehan, W.

The von Hippel-Lindau gene (VHL), composed of three exons, encodes a protein, pVHL, with diverse tumor suppressor activities. Germline VHL mutations are found in patients with von Hippel-Lindau (VHL), an autosomal dominant hereditary cancer syndrome in which affected individuals are at risk for the development of highly vascularized benign and malignant tumors including central nervous system hemangioblastomas, retinal hemangiomas, clear cell renal carcinomas (ccRCCs), pheochromocytomas, and [...]

Menée in vivo, cette étude met en évidence divers mécanismes par lesquels la mutation P81S du gène VHL favorise la croissance d'un carcinome rénal à cellules claires associé à une exposition professionelle au trichloroéthylène

Pleiotropic Effects of the Trichloroethylene-Associated P81S VHL Mutation on Metabolism, Apoptosis, and ATM-Mediated DNA Damage Response

DeSimone, Michelle C. ; Rathmell, W. Kimryn ; Threadgill, David W.

Background The risk relevance of the P81S von Hippel-Lindau (VHL) gene hotspot mutation identified in clear cell renal cell carcinoma from individuals exposed occupationally to trichloroethylene (TCE) is not known. VHL mutations in hereditary VHL syndrome strongly correlate with phenotypic associations, but specific sporadic mutations in VHL that uniquely alter its protein function may provide a selective growth advantage for somatic cells harboring these mutations. Methods VHL deficient (Vhl [...]

Menée à l'aide d'un modèle murin de leucémie lymphoïde aiguë, cette étude met en évidence des mécanismes par lesquels, en l'absence du suppresseur de tumeurs p16INK4a, la kinase CDK6 favorise la prolifération cellulaire et l'angiogenèse

The Kinase-Independent, Second Life of CDK6 in Transcription

Otto, Tobias ; Sicinski, Piotr

CDK6 is an oncogenic kinase regulating the cell cycle. In this issue of Cancer Cell, Kollmann and colleagues demonstrate that CDK6 performs a kinase-independent transcriptional function in regulating expression of VEGF-A and p16INK4a. These observations link the cell cycle machinery and angiogenesis and reveal the presence of a fail-safe antiproliferative mechanism.

Menée à l'aide d'un modèle murin de leucémie lymphoïde aiguë, cette étude met en évidence des mécanismes par lesquels, en l'absence du suppresseur de tumeurs p16INK4a, la kinase CDK6 favorise la prolifération cellulaire et l'angiogenèse

A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis

Kollmann, Karoline ; Heller, Gerwin ; Schneckenleithner, Christine ; Warsch, Wolfgang ; Scheicher, Ruth ; Ott, Rene G ; Schäfer, Markus ; Fajmann, Sabine ; Schlederer, Michaela ; Schiefer, Ana-Iris ; Reichart, Ursula ; Mayerhofer, Matthias ; Hoeller, Christoph ; Zöchbauer-Müller, Sabine ; Kerjaschki, Dontscho ; Bock, Christoph ; Kenner, Lukas ; Hoefler, Gerald ; Freissmuth, Michael ; Green, Anthony R ; Moriggl, Richard ; Busslinger, Meinrad ; Malumbres, Marcos ; Sexl, Veronika

In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6 s kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, dans le micro-environnement d'une tumeur primitive du sein triplement négative, des fibroblastes associés au cancer favorisent le développement de métastases osseuses

Selection of Bone Metastasis Seeds by Mesenchymal Signals in the Primary Tumor Stroma

Zhang, Xiang H F. ; Jin, Xin ; Malladi, Srinivas ; Zou, Yilong ; Wen, Yong H ; Brogi, Edi ; Smid, Marcel ; Foekens, John A. ; Massagué, Joan

How organ-specific metastatic traits arise in primary tumors remains unknown. Here, we show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXCL12 and IGF1. Limiting concentrations of these factors select for cancer cells with high Src activity, a known [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, dans le micro-environnement d'une tumeur primitive du sein triplement négative, des fibroblastes associés au cancer favorisent le développement de métastases osseuses

Breast Cancer Bone Metastases: It s All about the Neighborhood

Guise, Theresa A

In order to establish themselves in distal sites, metastatic cancer cells need to acquire organ-specific traits. Zhang et al. provide evidence in breast cancer that a tumor cell's acquisition of properties for successful bone metastasis is influenced by signals from the stroma of the primary tumor.

Cet article passe en revue les perspectives offertes par les plateformes d'analyse protéomique à l'échelle d'une seule cellule pour l'étude des réseaux de signalisation dans le cancer

Microchip platforms for multiplex single-cell functional proteomics with applications to immunology and cancer research

Wei, Wei ; Shin, Young ; Ma, Chao ; Wang, Jun ; Elitas, Meltem ; Fan, Rong ; Heath, James

Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing approaches for directly elucidating phosphoprotein signaling networks in cancer cells or for capturing high-resolution snapshots of immune system function in patients with various disease conditions. We discuss advances in single-cell proteomics [...]

Cet article passe en revue les perspectives offertes par les plateformes d'analyse protéomique à l'échelle d'une seule cellule pour l'étude des réseaux de signalisation dans le cancer

Single-cell analysis: toward the clinic

Speicher, Michael

Human life starts with a single cell, the zygote, which undergoes multiple mitotic cell divisions to form a complete body. During each cell division, the genome has to be replicated to form the approximately 1014 cells that make up the adult human body. For a long time, it was thought that all cells from the same individual harbored identical genomes. The only known exceptions being lymphocytes, in which antigen- and pathogen-driven recombination and hypermutation generate genetic diversity, [...]