Menée à l'aide de lignées cellulaires de glioblastome, d'échantillons tumoraux prélevés sur des patients et de modèles murins, cette étude met en évidence un mécanisme par lequel le facteur de transcription E2F7 favorise la prolifération cellulaire, le processus métastatique et la tumorigenèse via la régulation des voies PTEN/AKT/mTOR par la méthyltransférase EZH2

E2F7−EZH2 axis regulates PTEN/AKT/mTOR signalling and glioblastoma progression

Yang, Rui ; Wang, Mei ; Zhang, Guanghui ; Bao, Yonghua ; Wu, Yanan ; Li, Xiuxiu ; Yang, Wancai ; Cui, Hongjuan

Background: E2F transcription factors are considered to be important drivers of tumour growth. E2F7 is an atypical E2F factor, and its role in glioblastoma remains undefined. Methods: E2F7 expression was examined in patients by IHC and qRT-PCR. The overall survival probability was determined by statistical analyses. MTT assay, colony formation, cell-cycle assay, cell metastasis and the in vivo model were employed to determine the functional role of E2F7 in glioblastoma. Chromatin [...]

Menée à partir d'échantillons de tissus tumoraux et de tissus adjacents sains prélevés sur des patients atteints d'un carcinome hépatocellulaire et menée à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel la galectine-3 favorise le processus métastatique via l'activation de la signalisation de la bêta

Galectin-3 favours tumour metastasis via the activation of beta-catenin signalling in hepatocellular carcinoma

Song, Mengjia ; Pan, Qiuzhong ; Yang, Jieying ; He, Junyi ; Zeng, Jianxiong ; Cheng, Shaoyan ; Huang, Yue ; Zhou, Zi-Qi ; Zhu, Qian ; Yang, Chaopin ; Han, Yulong ; Tang, Yan ; Chen, Hao ; Weng, De-sheng ; Xia, Jian-chuan

Background : High probability of metastasis limited the long-term survival of patients with hepatocellular carcinoma (HCC). Our previous study revealed that Galectin-3 was closely associated with poor prognosis in HCC patients. Methods : The effects of Galectin-3 on tumour metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated. Results : Galectin-3 showed a close correlation with vascular invasion and [...]

Menée à l'aide de lignées de cellules cancéreuses, d'échantillons sériques humains et d'un modèle murin, cette étude met en évidence un mécanisme par lequel l'accumulation sérique de l'acide méthylmalonique induite par l'âge favorise la progression tumorale

Age-induced accumulation of methylmalonic acid promotes tumour progression

Gomes, Ana P. ; Ilter, Didem ; Low, Vivien ; Endress, Jennifer E. ; Fernández-García, Juan ; Rosenzweig, Adam ; Schild, Tanya ; Broekaert, Dorien ; Ahmed, Adnan ; Planque, Melanie ; Elia, Ilaria ; Han, Julie ; Kinzig, Charles ; Mullarky, Edouard ; Mutvei, Anders P. ; Asara, John ; de Cabo, Rafael ; Cantley, Lewis C. ; Dephoure, Noah ; Fendt, Sarah-Maria ; Blenis, John

The risk of cancer and associated mortality increases substantially in humans from the age of 65 years onwards1–6. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy2,3,7,8. For decades, this link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the established role of diet, exercise and small molecules that target the pace of metabolic ageing9–12. Here we show [...]

Menée à l'aide de lignées de cellules cancéreuses et de modèles murins, cette étude met en évidence un mécanisme par lequel l'hyperglycémie accroît l'échappement immunitaire de la tumeur en induisant la polarisation alternative des macrophages via l'augmentation de l'O-GlcNAcylation

Hyperglycemia Enhances Cancer Immune Evasion by Inducing Alternative Macrophage Polarization through Increased O-GlcNAcylation

Rodrigues Mantuano, Natália ; Stanczak, Michal A. ; Oliveira, Isadora de Araújo ; Kirchhammer, Nicole ; Filardy, Alessandra A. ; Monaco, Gianni ; Santos, Ronan Christian ; Fonseca, Agatha Carlos ; Fontes, Miguel ; Bastos, César de Souza ; Dias, Wagner B. ; Zippelius, Alfred ; Todeschini, Adriane R. ; Läubli, Heinz

Diabetes mellitus (DM) significantly increases the risk for cancer and cancer progression. Hyperglycemia is the defining characteristic of DM and tightly correlates with a poor prognosis in patients with cancer. The hexosamine biosynthetic pathway (HBP) is emerging as a pivotal cascade linking high glucose, tumor progression, and impaired immune function. Here we show that enhanced glucose flow through the HBP drives cancer progression and immune evasion by increasing O-GlcNAcylation in [...]

Menée à l'aide de modèles murins de mélanome, cette étude démontre que les cellules cancéreuses du liquide lymphatique sont protégées de la ferroptose

Lymph protects metastasizing melanoma cells from ferroptosis

Ubellacker, Jessalyn M. ; Tasdogan, Alpaslan ; Ramesh, Vijayashree ; Shen, Bo ; Mitchell, Evann C. ; Martin-Sandoval, Misty S. ; Gu, Zhimin ; McCormick, Michael L. ; Durham, Alison B. ; Spitz, Douglas R. ; Zhao, Zhiyu ; Mathews, Thomas P. ; Morrison, Sean J.

Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1–4; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph [...]

Menée à l'aide d'échantillons tumoraux prélevés sur des patientes atteintes d'un cancer épithélial de l'ovaire et menée à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel les neutrophiles associés à la tumeur, via l'activation de la protéine jagged-2, favorisent l'échappement immunitaire du microenvironnement tumoral induit par l'interleukine IL-8

Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer

Yang, Moran ; Zhang, Guodong ; Wang, Yiying ; He, Mengdi ; Xu, Qing ; Lu, Jiaqi ; Liu, Haiou ; Xu, Congjian

Background : Tumour associated neutrophils (TANs) play a controversial role in regulating immune surveillance and immune evasion in various malignancies. Here, we investigated the relevance of TANs with the prognosis and immune microenvironment of epithelial ovarian cancer (EOC). Methods : We characterised TANs using flow cytometric analysis and immunofluorescence analysis. The prognostic merit of TANs in EOC was evaluated using cox regression analysis. Furthermore, we explored the therapeutic [...]

Menée à partir de l'analyse d'échantillons biopsiques provenant de patients atteints d'un glioblastome et menée à l'aide d'un modèle de simulation, cette étude met en évidence le rôle de l'hypoxie dans la vitesse d'évolution de la tumeur

Evidence for hypoxia increasing the tempo of evolution in glioblastoma

Grimes, David Robert ; Jansen, Marnix ; Macauley, Robert J. ; Scott, Jacob G. ; Basanta, David

Background : Tumour hypoxia is associated with metastatic disease, and while there have been many mechanisms proposed for why tumour hypoxia is associated with metastatic disease, it remains unclear whether one precise mechanism is the key reason or several in concert. Somatic evolution drives cancer progression and treatment resistance, fuelled not only by genetic and epigenetic mutation but also by selection from interactions between tumour cells, normal cells and physical micro-environment. [...]

A partir de l'analyse de données de séquençage du génome entier de 3 212 patients atteints d'un cancer, cette étude met en évidence une association entre ADN extrachromosomique, amplification d'oncogènes et pronostic défavorable

Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers

Kim, Hoon ; Nguyen, Nam-Phuong ; Turner, Kristen ; Wu, Sihan ; Gujar, Amit D. ; Luebeck, Jens ; Liu, Jihe ; Deshpande, Viraj ; Rajkumar, Utkrisht ; Namburi, Sandeep ; Amin, Samirkumar B. ; Yi, Eunhee ; Menghi, Francesca ; Schulte, Johannes H. ; Henssen, Anton G. ; Chang, Howard Y. ; Beck, Christine R. ; Mischel, Paul S. ; Bafna, Vineet ; Verhaak, Roel G. W.

Extrachromosomal DNA (ecDNA) amplification promotes intratumoral genetic heterogeneity and accelerated tumor evolution1–3; however, its frequency and clinical impact are unclear. Using computational analysis of whole-genome sequencing data from 3,212 cancer patients, we show that ecDNA amplification frequently occurs in most cancer types but not in blood or normal tissue. Oncogenes were highly enriched on amplified ecDNA, and the most common recurrent oncogene amplifications arose on ecDNA. [...]