Menée in vitro et à l'aide de modèles murins, cette étude démontre que l'oxydation de l'ubiquinol mitochondrial est nécessaire à la croissance tumorale

Mitochondrial ubiquinol oxidation is necessary for tumour growth

Martínez-Reyes, Inmaculada ; Cardona, Luzivette Robles ; Kong, Hyewon ; Vasan, Karthik ; McElroy, Gregory S. ; Werner, Marie ; Kihshen, Hermon ; Reczek, Colleen R. ; Weinberg, Samuel E. ; Gao, Peng ; Steinert, Elizabeth M. ; Piseaux, Raul ; Budinger, G. R. Scott ; Chandel, Navdeep S.

The mitochondrial electron transport chain (ETC) is necessary for tumour growth1–6 and its inhibition has demonstrated anti-tumour efficacy in combination with targeted therapies7–9. Furthermore, human brain and lung tumours display robust glucose oxidation by mitochondria10,11. However, it is unclear why a functional ETC is necessary for tumour growth in vivo. ETC function is coupled to the generation of ATP—that is, oxidative phosphorylation and the production of metabolites by the [...]

Menée in vitro sur un modèle tridimensionnel de cancer colorectal, cette étude met en évidence le rôle des fibroblastes associés au cancer dans la progression de la maladie et le remodelage du stroma tumoral

Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma

Pape, Judith ; Magdeldin, Tarig ; Stamati, Katerina ; Nyga, Agata ; Loizidou, Marilena ; Emberton, Mark ; Cheema, Umber

Background : Cancer-associated fibroblasts (CAFs) are highly differentiated and heterogeneous cancer-stromal cells that promote tumour growth, angiogenesis and matrix remodelling. Methods : We utilised an adapted version of a previously developed 3D in vitro model of colorectal cancer, composed of a cancer mass and the surrounding stromal compartment. We compared cancer invasion with an acellular stromal surround, a “healthy” or normal cellular stroma and a cancerous stroma. For the cancerous [...]

Menée à l'aide de modèles murins de cancer du sein et à partir de données portant sur des patientes, cette étude met en évidence un mécanisme par lequel un infarctus du myocarde accélère la croissance tumorale en favorisant la modification du phénotype de monocytes de la moelle osseuse

Myocardial infarction accelerates breast cancer via innate immune reprogramming

Koelwyn, Graeme J. ; Newman, Alexandra A. C. ; Afonso, Milessa S. ; van Solingen, Coen ; Corr, Emma M. ; Brown, Emily J. ; Albers, Kathleen B. ; Yamaguchi, Naoko ; Narke, Deven ; Schlegel, Martin ; Sharma, Monika ; Shanley, Lianne C. ; Barrett, Tessa J. ; Rahman, Karishma ; Mezzano, Valeria ; Fisher, Edward A. ; Park, David S. ; Newman, Jonathan D. ; Quail, Daniela F. ; Nelson, Erik R. ; Caan, Bette J. ; Jones, Lee W. ; Moore, Kathryn J.

Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1 or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3–5. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial [...]

Menée à l'aide d'un modèle de poisson-zèbre, cette étude met en évidence un mécanisme par lequel la perte de l'expression du gène ARID1A dans les cellules de neuroblastome favorise l'acquisition d'un phénotype plus agressif

ARID1A loss in neuroblastoma promotes the adrenergic-to-mesenchymal transition by regulating enhancer-mediated gene expression

Shi, Hui ; Tao, Ting ; Abraham, Brian J. ; Durbin, Adam D. ; Zimmerman, Mark W. ; Kadoch, Cigall ; Look, A. Thomas

Mutations in genes encoding SWI/SNF chromatin remodeling complexes are found in approximately 20% of all human cancers, with ARID1A being the most frequently mutated subunit. Here, we show that disruption of ARID1A homologs in a zebrafish model accelerates the onset and increases the penetrance of MYCN-driven neuroblastoma by increasing cell proliferation in the sympathoadrenal lineage. Depletion of ARID1A in human NGP neuroblastoma cells promoted the adrenergic-to-mesenchymal transition with [...]

Menée à partir de 33 échantillons tumoraux fixés au formaldéhyde et inclus en paraffine après prélèvement sur 31 patients atteints d'un carcinome fibrolamellaire du foie (âge médian au diagnostic : 18 ans), cette étude analyse le profil moléculaire et les anomalies génétiques de ce type de tumeur pour identifier des cibles thérapeutiques potentielles

Molecular profiling and analysis of genetic aberrations aimed at identifying potential therapeutic targets in fibrolamellar carcinoma of the liver

El Dika, Imane ; Bowman, Anita S. ; Berger, Michael F. ; Capanu, Marinela ; Chou, Joanne F. ; Benayed, Ryma ; Zehir, Ahmet ; Shia, Jinru ; O’Reilly, Eileen M. ; Klimstra, David S. ; Solit, David B. ; Abou-Alfa, Ghassan K.

Background : Fibrolamellar carcinoma (FLC) is a rare primary liver cancer of young adults. A functional chimeric transcript resulting from the in‐frame fusion of the DNAJ homolog, subfamily B, member 1 (DNAJB1 ), and the catalytic subunit of protein kinase A (PRKACA ) genes on chromosome 19 is believed to be unique in FLC, with a possible role in pathogenesis, yet with no established therapeutic value. The objective of the current study was to understand the molecular landscape of FLC and to [...]

Menée à partir de données du projet "The Cancer Genome Atlas" et à partir de l'analyse de réseaux de régulation de gènes, cette étude met en évidence un mécanisme d'immunotolérance impliquant des glycoprotéines spécifiques de la grossesse

Functional network analysis reveals an immune tolerance mechanism in cancer

Mathews, James C. ; Nadeem, Saad ; Pouryahya, Maryam ; Belkhatir, Zehor ; Deasy, Joseph O. ; Levine, Arnold J. ; Tannenbaum, Allen R.

A major problem in data science is representation of data so that the variables driving key functions can be uncovered and explored. Correlation analysis is widely used to simplify networks of feature variables by reducing redundancies, but makes limited use of the network topology, relying on comparison of direct neighbor variables. The proposed method incorporates relational or functional profiles of neighboring variables along multiple common neighbors, which are fitted with Gaussian mixture [...]

Menée à partir du séquençage de l'ensemble du génome et du transcriptome de 100 métastases prostatiques résistantes à la castration, cette étude analyse le profil de méthylation de l'ADN et de l'ARN des cellules cancéreuses

The DNA methylation landscape of advanced prostate cancer

Zhao, Shuang G. ; Chen, William S. ; Li, Haolong ; Foye, Adam ; Zhang, Meng ; Sjöström, Martin ; Aggarwal, Rahul ; Playdle, Denise ; Liao, Arnold ; Alumkal, Joshi J. ; Das, Rajdeep ; Chou, Jonathan ; Hua, Junjie T. ; Barnard, Travis J. ; Bailey, Adina M. ; Chow, Eric D. ; Perry, Marc D. ; Dang, Ha X. ; Yang, Rendong ; Moussavi-Baygi, Ruhollah ; Zhang, Li ; Alshalalfa, Mohammed ; Laura Chang, S. ; Houlahan, Kathleen E. ; Shiah, Yu-Jia ; Beer, Tomasz M. ; Thomas, George ; Chi, Kim N. ; Gleave, Martin ; Zoubeidi, Amina ; Reiter, Robert E. ; Rettig, Matthew B. ; Witte, Owen ; Yvonne Kim, M. ; Fong, Lawrence ; Spratt, Daniel E. ; Morgan, Todd M. ; Bose, Rohit ; Huang, Franklin W. ; Li, Hui ; Chesner, Lisa ; Shenoy, Tanushree ; Goodarzi, Hani ; Asangani, Irfan A. ; Sandhu, Shahneen ; Lang, Joshua M. ; Mahajan, Nupam P. ; Lara, Primo N. ; Evans, Christopher P. ; Febbo, Phillip ; Batzoglou, Serafim ; Knudsen, Karen E. ; He, Housheng H. ; Huang, Jiaoti ; Zwart, Wilbert ; Costello, Joseph F. ; Luo, Jianhua ; Tomlins, Scott A. ; Wyatt, Alexander W. ; Dehm, Scott M. ; Ashworth, Alan ; Gilbert, Luke A. ; Boutros, Paul C. ; Farh, Kyle ; Chinnaiyan, Arul M. ; Maher, Christopher A. ; Small, Eric J. ; Quigley, David A. ; Feng, Felix Y.

Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype [...]

A partir de l'analyse du microenvironnement de tumeurs cérébrales, cette étude démontre que le profil des cellules immunitaires infiltrantes varie en fonction des caractéristiques de la tumeur (gliome avec ou sans mutation de l'isocitrate déshydrogénase, métastases cérébrales)

Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Klemm, Florian ; Maas, Roeltje R. ; Bowman, Robert L. ; Kornete, Mara ; Soukup, Klara ; Nassiri, Sina ; Brouland, Jean-Philippe ; Iacobuzio-Donahue, Christine A. ; Brennan, Cameron ; Tabar, Viviane ; Gutin, Philip H. ; Daniel, Roy T. ; Hegi, Monika E. ; Joyce, Johanna A.

Brain malignancies encompass a range of primary and metastatic cancers, including low-grade and high-grade gliomas and brain metastases (BrMs) originating from diverse extracranial tumors. Our understanding of the brain tumor microenvironment (TME) remains limited, and it is unknown whether it is sculpted differentially by primary versus metastatic disease. We therefore comprehensively analyzed the brain TME landscape via flow cytometry, RNA sequencing, protein arrays, culture assays, and [...]