Menée sur 81 échantillons tumoraux fixés au formol et inclus en paraffine après prélèvement sur des patients atteints d'un cancer du poumon non à petites cellules, cette étude identifie la présence de mutations de gènes des récepteurs aux éphrines en association avec des mutations de divers gènes d'intérêt clinique connu

Mutated Ephrin Receptor Genes in Non-Small Cell Lung Carcinoma and Their Occurrence with Driver Mutations—Targeted Resequencing Study on Formalin-Fixed, Paraffin-Embedded Tumor Material of 81 Patients

Mäki-Nevala, Satu ; Kaur Sarhadi, Virinder ; Tuononen, Katja ; Lagström, Sonja ; Ellonen, Pekka ; Rönty, Mikko ; Wirtanen, Aino ; Knuuttila, Aija ; Knuutila, Sakari

Non-small cell lung carcinoma (NSCLC) is the most common subtype of lung cancer. The oncogenic potential of receptor tyrosine kinases (RTKs) is widely known and they are potential targets for tailored therapy. Ephrin receptors (Ephs) form the largest group of RTKs. Nevertheless, Ephs are not widely studied in NSCLC so far. The aim of our study was to investigate novel mutations of Eph genes (EPHA1–8, EPHB1–4, EPHB6) and their association with clinically relevant mutations in BRAF, EML4-ALK, [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels des cellules surexprimant le facteur de transcription Sox2 sont susceptibles d'induire une tumeur de l'hypophyse

Sox2+ Stem/Progenitor Cells in the Adult Mouse Pituitary Support Organ Homeostasis and Have Tumor-Inducing Potential

Andoniadou, Cynthia Lilian ; Matsushima, Danielle ; Mousavy Gharavy, Seyedeh Neda ; Signore, Massimo ; Mackintosh, Albert Ian ; Schaeffer, Marie ; Gaston-Massuet, Carles ; Mollard, Patrice ; Jacques, Thomas Stanley ; Le Tissier, Paul ; Dattani, Mehul Tulsidas ; Pevny, Larysa Halyna ; Martinez-Barbera, Juan Pedro

Sox2+ adult mouse pituitary cells can self-renew and terminally differentiate in vitro, but their physiological role in vivo and possible contribution to oncogenesis remain largely unknown. Using genetic lineage tracing, we show here that the Sox2+ cell compartment of both the embryonic and adult pituitary contains stem/progenitor cells that are able to differentiate into all hormone-producing lineages and contribute to organ homeostasis during postnatal life. In addition, we show that targeted [...]

Menée sur des lignées cellulaires de cancer du poumon non à petites cellules, cette étude met en évidence des mécanismes permettant de rendre compte de la diminution de l'expression de la protéine codée par le gène suppresseur de tumeurs DLC1 dans des cellules exprimant l'ARN messager de ce gène

CRL4A-FBXW5–mediated degradation of DLC1 Rho GTPase-activating protein tumor suppressor promotes non-small cell lung cancer cell growth

Kim, Tai Young ; Jackson, Sarah ; Xiong, Yue ; Whitsett, Timothy G. ; Lobello, Janine R. ; Weiss, Glen J. ; Tran, Nhan Le ; Bang, Yung-Jue ; Der, Channing J.

DLC1 encodes a RhoA GTPase-activating protein and tumor suppressor lost in cancer by genomic deletion or epigenetic silencing and loss of DLC1 gene transcription. We unexpectedly identified non-small cell lung cancer (NSCLC) cell lines and tumor tissue that expressed DLC1 mRNA yet lacked DLC1 protein expression. We determined that DLC1 was ubiquitinated and degraded by cullin 4A–RING ubiquitin ligase (CRL4A) complex interaction with DDB1 and the FBXW5 substrate receptor. siRNA-mediated [...]

Menée à l'aide de modèles murins, cette étude suggère que l'expression d'un facteur de différenciation musculaire, MyoD, dans le cervelet contribue à inhiber le développement d'un médulloblastome

MyoD is a tumor suppressor gene in Medulloblastoma

Dey, Joyoti ; Dubuc, Adrian M. ; Pedro, Kyle D ; Thirstrup, Derek ; Mecham, Brigham H ; Northcott, Paul ; Wu, Xiaochong ; Shih, David J. ; Tapscott, Stephen J. ; LeBlanc, Michael L. ; Taylor, Michael D. ; Olson, James M.

While medulloblastoma, a pediatric tumor of the cerebellum, is characterized by aberrations in developmental pathways, the majority of genetic determinants remain unknown. An unbiased Sleeping Beauty transposon screen revealed MyoD as a putative medulloblastoma tumor suppressor. This was unexpected, as MyoD is a muscle differentiation factor and not previously known to be expressed in cerebellum or medulloblastoma. In response to deletion of one allele of MyoD, two other Sonic hedgehog-driven [...]

Cet article passe en revue les travaux récents sur le rôle des isoformes de la famille des kinases RSK dans le processus métastatique

RSK Isoforms in Cancer Cell Invasion and Metastasis

Sulzmaier, Florian J. ; Ramos, Joe W.

Metastasis, the spreading of cancer cells from a primary tumor to secondary sites throughout the body, is the primary cause of death for patients with cancer. New therapies that prevent invasion and metastasis in combination with current treatments could therefore significantly reduce cancer recurrence and morbidity. Metastasis is driven by altered signaling pathways that induce changes in cell–cell adhesion, the cytoskeleton, integrin function, protease expression, epithelial-to-mesenchymal [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant la production mitochondriale d'espèces réactives de l'oxygène, le facteur induit par l'hypoxie HIF-2

HIF-2

Rouault-Pierre, Kevin ; Lopez-Onieva, Lourdes ; Foster, Katie ; Anjos-Afonso, Fernando ; Lamrissi-Garcia, Isabelle ; Serrano-Sanchez, Martin ; Mitter, Richard ; Ivanovic, Zoran ; de Verneuil, Hubert ; Gribben, John ; Taussig, David ; Rezvani, Hamid Reza ; Mazurier, Frédéric ; Bonnet, Dominique

Hematopoietic stem and progenitor cells (HSPCs) are exposed to low levels of oxygen in the bone marrow niche, and hypoxia-inducible factors (HIFs) are the main regulators of cellular responses to oxygen variation. Recent studies using conditional knockout mouse models have unveiled a major role for HIF-1

Menée in vitro et in silico, cette étude présente un modèle de simulation rendant compte du rôle des fibroblastes sénescents dans la progression d'un mélanome

Senescent fibroblasts in melanoma initiation and progression: an integrated theoretical, experimental, and clinical approach

Kim, Eunjung ; Rebecca, Vito W ; Fedorenko, Inna V ; Messina, Jane L. ; Mathew, Rahel ; Maria-Engler, Silvya S ; Basanta, David ; Smalley, Keiran S.M. ; Anderson, Alexander RA

We present an integrated study to understand the key role of senescent fibroblasts in driving melanoma progression. Based on the hybrid cellular automata paradigm we developed an in silico model of normal skin. The model focuses on key cellular and microenvironmental variables that regulate interactions among keratinocytes, melanocytes and fibroblasts, key components of the skin. The model recapitulates normal skin structure, and is robust enough to withstand physical as well as biochemical [...]

Menée à l'aide d'un modèle murin de cancer du pancréas, cette étude met en évidence des mécanismes par lesquels, en interagissant avec l'oncogène Kras, l'interleukine 6 favorise la progression tumorale

Interleukin-6 Is Required for Pancreatic Cancer Progression by Promoting MAPK Signaling Activation and Oxidative Stress Resistance

Zhang, Yaqing ; Yan, Wei ; Collins, Meredith A. ; Bednar, Filip ; Rakshit, Sabita ; Zetter, Bruce R. ; Stanger, Ben Z. ; Chung, Ivy ; Rhim, Andrew D. ; di Magliano, Marina Pasca

Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multiple cell types within the tumor microenvironment. Here, we show that IL-6 is required for the maintenance and progression of pancreatic cancer precursor lesions. In fact, the lack [...]

Menée sur des lignées cellulaires de cancer de la prostate, cette étude met en évidence des mécanismes par lesquels, via la régulation des interactions entre les nerfs du microenvironnement tumoral et les cellules cancéreuses, la sémaphorine 4F favorise la progression tumorale

Semaphorin 4F as a Critical Regulator of Neuro-Epithelial Interactions and a Biomarker of Aggressive Prostate Cancer

Ding, Yi ; He, Dandan ; Florentin, Diego ; Frolov, Anna ; Hilsenbeck, Susan G. ; Ittmann, Michael M. ; Kadmon, Dov ; Miles, Brian ; Rowley, David R. ; Ayala, Gustavo E.

BACKGROUND: Semaphorin 4F (S4F) has roles in embryological axon guidance and is expressed in adults. S4F is involved in cancer-induced neurogenesis. METHODS: Prostate cells were transfected with S4F retrovirus. Cells and controls were used for a BrdU incorporation assay (proliferation) and in vitro scratch and matrigel transwell chamber invasion assay (migration). Monoclonal antibodies were developed using baculovirus expressed recombinant GST-S4F and used to immunostain tissue microarrays. [...]

A partir d'une analyse de 105 échantillons tumoraux prélevés sur des patientes atteintes d'un cancer du sein, puis in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant de façon négative l'expression du gène TWIST1, le micro-ARN 720 inhibe les processus invasif et métastatique

miR-720 inhibits tumor invasion and migration in breast cancer by targeting TWIST1

Li, Lin-Zi ; Zhang, Chris Zhiyi ; Liu, Li-Li ; Yi, Chun ; Lu, Shi-Xun ; Zhou, Xuan ; Zhang, Zhao-Jie ; Peng, Yi-Han ; Yang, Yuan-Zhong ; Yun, Jing-Ping

Breast cancer is the leading cause of cancer death among females, with tumor metastasis being primarily responsible for breast cancer-associated mortality. Current literatures have shown that microRNAs are implicated in tumor metastasis. In this study, we found that the expression of miR-720 was significantly down-regulated in primary breast cancer, with greater down-regulation in metastatic tumors. Statistical analysis of 105 cases of primary human breast cancer demonstrated that decreased [...]