Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude montre que des cellules ne comportant que des copies uniques des gènes mutés KRAS et PIK3CA sont susceptibles d'induire la formation d'une tumeur

Single copies of mutant KRAS and mutant PIK3CA cooperate in immortalized human epithelial cells to induce tumor formation

Wang, Grace M. ; Wong, Hong-Yuen ; Konishi, Hiroyuki ; Blair, Brian G. ; Abukhdeir, Abde ; Gustin, John P. ; Rosen, D. Marc ; Denmeade, Samuel ; Rasheed, Zeshaan ; Matsui, William ; Garay, Joseph P. ; Mohseni, Morassa ; Higgins, Michaela J. ; Cidado, Justin ; Jelovac, Danijela ; Croessmann, Sarah ; Cochran, Rory ; Karnan, Sivasundaram ; Konishi, Yuko ; Ota, Akinobu ; Hosokawa, Yoshitaka ; Argani, Pedram ; Lauring, Josh ; Park, Ben Ho

The selective pressures leading to cancers with mutations in both KRAS and PIK3CA are unclear. Here we demonstrate that somatic cell knock in of both KRAS G12V and oncogenic PIK3CA mutations in human breast epithelial cells results in cooperative activation of the PI3 Kinase and MAP Kinase pathways in vitro, and leads to tumor formation in immunocompromised mice. Xenografts from double knock in cells retain single copies of mutant KRAS and PIK3CA suggesting that tumor formation does not require [...]

Menée sur des échantillons de sang ou de moelle osseuse prélevés sur 54 patients atteints d'une leucémie myéloïde aiguë récemment diagnostiquée, cette étude analyse les anomalies génomiques présentes sur le chromosome 11 en dehors de la région 11q23.3 du proto-oncogène MLL

Characterization of chromosome 11 breakpoints and the areas of deletion and amplification in patients with newly diagnosed acute myeloid leukemia

Sarova, Iveta ; Brezinova, Jana ; Zemanova, Zuzana ; Bystricka, Dagmar ; Krejcik, Zdenek ; Soukup, Petr ; Vydra, Jan ; Cermak, Jaroslav ; Jonasova, Anna ; Michalova, Kyra

Chromosome 11 abnormalities are found in many hematological malignancies. In acute myeloid leukemia (AML), a proto-oncogene MLL (11q23.3) is frequently altered. However, rearrangements involving other regions of chromosome 11 have been reported. Therefore, we have characterized the chromosome 11 breakpoints and common deleted and amplified areas in the bone marrow or peripheral blood cells of newly diagnosed patients with AML. Using molecular–cytogenetic methods (multicolor fluorescence in situ [...]

Cette étude évalue le niveau de raccourcissement des télomères et d'instabilité génomique dans des échantillons prélevés sur 51 patientes présentant des mutations BRCA1 ou BRCA2 et atteintes d'une dysplasie tubo-ovarienne, sur 12 patientes atteintes d'un carcinome intrépithélial tubaire séreux, 53 patientes atteintes d'un carcinome séreux tubo-ovarien de haut grade et 36 témoins

Early telomere shortening and genomic instability in tubo-ovarian preneoplastic lesions

Chene, Gautier ; Tchirkov, Andrei ; Pierre-Eymard, Eleonore ; Dauplat, Jacques ; Raoelfils, Ines ; Cayre, Anne ; Watkin, Emmanuel ; Vago, Philippe ; Penault Llorca, Frederique

Purpose: Genetic instability plays an important role in ovarian carcinogenesis. We investigated the level of telomere shortening and genomic instability in early and pre-invasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC) and tubo-ovarian dysplasia (TOD). 51 TOD from prophylactic salpingo-oophorectomies with BRCA 1 or 2 mutation, 12 STICs, 53 tubo-ovarian high grade serous carcinoma and 36 non-cancerous controls were laser-capture microdissected from formalin-fixed [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels, en favorisant la sécrétion de divers facteurs du microenvironnement, la protéine p53 joue son rôle de suppresseur de tumeurs

Non-Cell-Autonomous Tumor Suppression by p53

Lujambio, Amaia ; Akkari, Leila ; Simon, Janelle ; Grace, Danielle ; Tschaharganeh, Darjus F ; Bolden, Jessica E ; Zhao, Zhen ; Thapar, Vishal ; Joyce, Johanna A ; Krizhanovsky, Valery ; Lowe, Scott W

The p53 tumor suppressor can restrict malignant transformation by triggering cell-autonomous programs of cell-cycle arrest or apoptosis. p53 also promotes cellular senescence, a tumor-suppressive program that involves stable cell-cycle arrest and secretion of factors that modify the tissue microenvironment. In the presence of chronic liver damage, we show that ablation of a p53-dependent senescence program in hepatic stellate cells increases liver fibrosis and cirrhosis associated with reduced [...]

A partir de données portant sur l'expression de gènes du métabolisme dans 22 différents types de tumeurs, cette étude met en évidence une hétérogénéité à tous les niveaux du réseau métabolique et identifie des isoenzymes dont l'expression est spécifiquement altérée dans les cellules tumorales

Heterogeneity of tumor-induced gene expression changes in the human metabolic network

Hu, Jie ; Locasale, Jason W. ; Bielas, Jason H. ; O'Sullivan, Jacintha ; Sheahan, Kieran ; Cantley, Lewis C. ; Heiden, Matthew G. Vander ; Vitkup, Dennis

Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how the expression of metabolic genes in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression [...]

Menée sur 188 échantillons tumoraux prélevés sur des patients atteints d'un médulloblastome, puis in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels le facteur de transcription Sox2 favorise la prolifération des cellules tumorales

Sox2 requirement in Sonic hedgehog-associated medulloblastoma

Ahlfeld, Julia ; Favaro, Rebecca ; Pagella, Pierfrancesco ; Kretzschmar, Hans A ; Nicolis, Silvia ; Schüller, Ulrich

The transcription factor Sox2 has been demonstrated to play essential roles during embryonic development as well as in cancer. In order to more precisely understand tumor biology and to identify potential therapeutical targets we thoroughly investigated the expression and function of Sox2 in medulloblastoma, a malignant embryonic brain tumor that initiates in the posterior fossa and eventually spreads throughout the entire cerebrospinal axis. We examined a large series of tumor samples (n=188) [...]

Cet artcle passe en revue les travaux récents sur le rôle des voies de signalisation du métabolisme du fer dans les différentes étapes du développement d'un cancer

Iron and cancer: more ore to be mined

Torti, Suzy V. ; Torti, Frank M.

Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central [...]

Menée à l'aide d'un dispositif de microfluidique, cette étude met en évidence des caractéristiques physiques (déformabilité, frottement...) spécifiques de cellules tumorales dotées d'un pouvoir métastatique

Characterizing deformability and surface friction of cancer cells

Byun, Sangwon ; Son, Sungmin ; Amodei, Dario ; Cermak, Nathan ; Shaw, Josephine ; Kang, Joon Ho ; Hecht, Vivian C. ; Winslow, Monte M. ; Jacks, Tyler ; Mallick, Parag ; Manalis, Scott R.

Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by the physical properties of the cells as well as their interactions with the confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro by measuring the time required for cells to pass through a constriction. Although a cell’s passage time is expected to depend on its deformability, measurements from existing approaches are confounded by a cell's size and its [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels la protéine DOCK1 favorise le processus métastatique d'un cancer du sein HER2+

Rac-specific guanine nucleotide exchange factor DOCK1 is a critical regulator of HER2-mediated breast cancer metastasis

Laurin, Mélanie ; Huber, Jennifer ; Pelletier, Ariane ; Houalla, Tarek ; Park, Morag ; Fukui, Yoshinori ; Haibe-Kains, Benjamin ; Muller, William J. ; Côté, Jean-François

Progression of solid tumors to the metastatic stage is accountable for the majority of cancer-related deaths. Further understanding of the molecular mechanisms governing metastasis is essential for the development of antimetastatic regimens. Here, we aimed to identify Rac activators that could promote metastasis downstream of human epithelial growth factor receptor 2 (HER2). We investigated if Dedicator of Cytokinesis 1 (DOCK1), based on its evolutionarily conserved role in receptor tyrosine [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant l'expression de FHL3, le gène PCBP2 favorise la progression d'un gliome

RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3

Han, Wei ; Xin, Zhongshuai ; Zhao, Zhiqiang ; Bao, Wen ; Lin, Xihua ; Yin, Bin ; Zhao, Jizong ; Yuan, Jiangang ; Qiang, Boqin ; Peng, Xiaozhong

PCBP2 is a member of the poly(C)-binding protein (PCBP) family, which plays an important role in posttranscriptional and translational regulation by interacting with single-stranded poly(C) motifs in target mRNAs. Several PCBP family members have been reported to be involved in human malignancies. Here, we show that PCBP2 is upregulated in human glioma tissues and cell lines. Knockdown of PCBP2 inhibited glioma growth in vitro and in vivo through inhibition of cell-cycle progression and [...]