Menée in vitro et à l'aide d'une xénogreffe sur un modèle murin de cancer de la prostate, cette étude met en évidence un mécanisme par lequel la cyclo-oxygénase COX-2, en agissant sur la signalisation de la prolactine du stroma tumoral, favorise la tumorigenèse

COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis

Zheng, Yu ; Comaills, Valentine ; Burr, Risa ; Boulay, Gaylor ; Miyamoto, David T. ; Wittner, Ben S. ; Emmons, Erin ; Sil, Srinjoy ; Koulopoulos, Michael W. ; Broderick, Katherine T. ; Tai, Eric ; Rengarajan, Shruthi ; Kulkarni, Anupriya S. ; Shioda, Toshi ; Wu, Chin-Lee ; Ramaswamy, Sridhar ; Ting, David T. ; Toner, Mehmet ; Rivera, Miguel N. ; Maheswaran, Shyamala ; Haber, Daniel A.

The documented efficacy of COX-2 inhibitors in cancer chemoprevention and in suppression of metastasis is predominantly attributed to inflammatory responses, whereas their effects on tumor-stromal interaction are poorly understood. Through single-cell transcriptome analyses in an immune-compromised mouse xenograft model and in vitro reconstitution experiments, we uncover a tumor-stromal paracrine pathway in which secretion by tumor cells of the COX-2 product prostaglandin E2 induces prolactin [...]

Menée in vitro et à l'aide d'une nouvelle approche statistique basée sur la comparaison des profils d'expression de l'ARN messager de la tumeur et du tissu sain adjacent, cette étude met en évidence le rôle du gène CBX2 dans le développement d'un carcinome mammaire invasif

A novel approach to modelling transcriptional heterogeneity identifies the oncogene candidate CBX2 in invasive breast carcinoma

Piqué, Daniel G. ; Montagna, Cristina ; Greally, John M. ; Mar, Jessica C.

Background : Oncogenes promote the development of therapeutic targets against subsets of cancers. Only several hundred oncogenes have been identified, primarily via mutation-based approaches, in the human genome. Transcriptional overexpression is a less-explored mechanism through which oncogenes can arise. Methods : Here, a new statistical approach, termed oncomix, which captures transcriptional heterogeneity in tumour and adjacent normal (i.e., tumour-free) mRNA expression profiles, was [...]

Menée in vitro sur des organoïdes de cellules épithéliales humaines et menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel le complexe PAR, dans les cellules ayant conservé leur polarité apicale/basale, inhibe la transition épithélio-mésenchymateuse et le développement de métastases en favorisant la dégradation du facteur de transcription SNAI1

Apical–basal polarity inhibits epithelial–mesenchymal transition and tumour metastasis by PAR-complex-mediated SNAI1 degradation

Jung, Hae-Yun ; Fattet, Laurent ; Tsai, Jeff H. ; Kajimoto, Taketoshi ; Chang, Qiang ; Newton, Alexandra C. ; Yang, Jing

Loss of apical–basal polarity and activation of epithelial–mesenchymal transition (EMT) both contribute to carcinoma progression and metastasis. Here, we report that apical–basal polarity inhibits EMT to suppress metastatic dissemination. Using mouse and human epithelial three-dimensional organoid cultures, we show that the PAR–atypical protein kinase C (aPKC) polarity complex inhibits EMT and invasion by promoting degradation of the SNAIL family protein SNAI1. Under intact apical–basal [...]

Menée in vitro et à l'aide de modèles murins de cancer métastatique du sein, cette étude montre que l'exposition chronique des cellules cancéreuses au TGF-beta stabilise la transition épithélio-mésenchymateuse, favorise la génération de cellules souches cancéreuses ainsi que la résistance thérapeutique, puis met en évidence la possibilité d'inhiber l'enzyme mTOR pour bloquer la tumorigenèse et lever la résistance thérapeutique

Chronic TGF-beta exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition

Katsuno, Yoko ; Meyer, Dominique Stephan ; Zhang, Ziyang ; Shokat, Kevan M. ; Akhurst, Rosemary J. ; Miyazono, Kohei ; Derynck, Rik

During cancer progression, cells gain the ability to move, invade, and adapt. Cells may gain these abilities through a process called “EMT” (epithelial-to-mesenchymal transition) that allows them to acquire properties of cancer stem-like cells (CSCs). Signaling by the growth factor TGF-β majorly contributes to EMT (see also the Review by Derynck and Budi), and EMT is generally accepted to be reversible as largely assessed in cell culture. To better mimic the patient context, Katsuno et al. [...]

Cet article passe en revue les données démontrant l'utilisation, lors du développement tumoral, de vaisseaux de tissus adjacents non cancéreux puis analyse les mécanismes moléculaires impliqués dans ce processus de cooptation vasculaire

Vessel co-option in cancer

Kuczynski, Elizabeth A. ; Vermeulen, Peter B. ; Pezzella, Francesco ; Kerbel, Robert S. ; Reynolds, Andrew R.

All solid tumours require a vascular supply in order to progress. Although the ability to induce angiogenesis (new blood vessel growth) has long been regarded as essential to this purpose, thus far, anti-angiogenic therapies have shown only modest efficacy in patients. Importantly, overshadowed by the literature on tumour angiogenesis is a long-standing, but continually emerging, body of research indicating that tumours can grow instead by hijacking pre-existing blood vessels of the surrounding [...]

A partir de l'analyse des données de la base "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer" et de la base "Ensembl genome database", cette étude met en évidence le caractère aléatoire, transitoire et non pathogène de la plupart des gènes de fusion détectés par séquençage à haut débit

Most gene fusions in cancer are stochastic events

Johansson, Bertil ; Mertens, Fredrik ; Schyman, Tommy ; Björk, Jonas ; Mandahl, Nils ; Mitelman, Felix

Cancer-associated gene fusions resulting in chimeric proteins or aberrant expression of one or both partner genes are pathogenetically and clinically important in several hematologic malignancies and solid tumors. Since the advent of different types of massively parallel sequencing (MPS), the number of identified gene fusions has increased dramatically, prompting the question whether they all have a biologic impact. By ascertaining the chromosomal locations of 8,934 genes involved in 10,861 [...]

Cet article analyse le rôle de la voie de signalisation du TGF-bêta dans l'hématopoïèse et les troubles myéloïdes, puis présente les traitements prometteurs contre les syndromes myélodysplasiques

The role of TGFβ in hematopoiesis and myeloid disorders

Bataller, Alex ; Montalban-Bravo, Guillermo ; Soltysiak, Kelly A. ; Garcia-Manero, Guillermo

The role of transforming growth factor-β (TGFβ) signaling in embryological development and tissue homeostasis has been thoroughly characterized. Its canonical downstream cascade is well known, even though its true complexity and other non-canonical pathways are still being explored. TGFβ signaling has been described as an important pathway involved in carcinogenesis and cancer progression. In the hematopoietic compartment, the TGFβ pathway is an important regulator of proliferation and [...]