Menée à l'aide d'un modèle murin de carcinome hépatocellulaire, cette étude met en évidence un mécanisme par lequel le microARN-206, en induisant la polarisation M1 des cellules de Kupffer, favorise le recrutement des lymphocytes T CD8+ et prévient la carcinogenèse

MicroRNA-206 promotes the recruitment of CD8+ T cells by driving M1 polarisation of Kupffer cells

Liu, Ningning ; Wang, Xiaomei ; Steer, Clifford John ; Song, Guisheng

Objective Kupffer cells (KCs) protect against hepatocellular carcinoma (HCC) by communicating with other immune cells. However, the underlying mechanism(s) of this process is incompletely understood.Design FVB/NJ mice were hydrodynamically injected with AKT/Ras and Sleeping Beauty transposon to induce HCC. Mini-circle and Sleeping Beauty were used to overexpress microRNA-206 in KCs of mice. Flow cytometry and immunostaining were used to evaluate the change in the immune system.Results [...]

Menée in vitro et in vivo, cette étude met en évidence un mécanisme par lequel l'accumulation de glycogène dans les cellules hépatiques pré-cancéreuses (via un processus de séparation de phase) favorise la carcinogenèse

Glycogen accumulation and phase separation drives liver tumor initiation

Liu, Qingxu ; Li, Jiaxin ; Zhang, Weiji ; Xiao, Chen ; Zhang, Shihao ; Nian, Cheng ; Li, Junhong ; Su, Dongxue ; Chen, Lihong ; Zhao, Qian ; Shao, Hui ; Zhao, Hao ; Chen, Qinghua ; Li, Yuxi ; Geng, Jing ; Hong, Lixin ; Lin, Shuhai ; Wu, Qiao ; Deng, Xianming ; Ke, Rongqin ; Ding, Jin ; Johnson, Randy L. ; Liu, Xiaolong ; Chen, Lanfen ; Zhou, Dawang

Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex [...]

Menée à partir du séquençage du génome entier de 150 patients adultes atteints d'une leucémie ou d'un lymphome à cellules T, cette étude identifie de nouvelles altérations génétiques impliquées dans le développement de ces maladies

Whole-genome landscape of adult T-cell leukemia/lymphoma

Kogure, Yasunori ; Kameda, Takuro ; Koya, Junji ; Yoshimitsu, Makoto ; Nosaka, Kisato ; Yasunaga, Jun-ichirou ; Imaizumi, Yoshitaka ; Watanabe, Mizuki ; Saito, Yuki ; Ito, Yuta ; McClure, Marni B ; Tabata, Mariko ; Shingaki, Sumito ; Yoshifuji, Kota ; Chiba, Kenichi ; Okada, Ai ; Kakiuchi, Nobuyuki ; Nannya, Yasuhito ; Kamiunten, Ayako ; Tahira, Yuki ; Akizuki, Keiichi ; Sekine, Masaaki ; Shide, Kotaro ; Hidaka, Tomonori ; Kubuki, Yoko ; Kitanaka, Akira ; Hidaka, Michihiro ; Nakano, Nobuaki ; Utsunomiya, Atae ; Sica, R. Alejandro ; Acuna-Villaorduna, Ana ; Janakiram, Murali ; Shah, Urvi A ; Ramos, Juan Carlos ; Shibata, Tatsuhiro ; Takeuchi, Kengo ; Takaori-Kondo, Akifumi ; Miyazaki, Yasushi ; Matsuoka, Masao ; Ishitsuka, Kenji ; Shiraishi, Yuichi ; Miyano, Satoru ; Ogawa, Seishi ; Ye, B.Hilda ; Shimoda, Kazuya ; Kataoka, Keisuke

Adult T-cell leukemia/lymphoma (ATL) is an aggressive neoplasm immunophenotypically resembling regulatory T cells, associated with human T-cell leukemia virus type-1. Here we performed whole-genome sequencing (WGS) of 150 ATL cases to reveal the overarching landscape of genetic alterations in ATL. We discovered frequent (33%) loss-of-function alterations preferentially targeting the CIC long isoform, which were overlooked by previous exome-centric studies of various cancer types. Long but not [...]

Menée in vitro et à l'aide d'une xénogreffe de cancer colorectal sur un modèle murin, cette étude met en évidence un mécanisme par lequel la protéine matricielle mitochondriale C14orf159 réduit le processus métastatique en supprimant la voie de signalisation des protéines Wnt et de la bêta-caténine

Mitochondrial matrix protein C14orf159 attenuates colorectal cancer metastasis by suppressing Wnt/beta-catenin signalling

Ohshima, Kenji ; Oi, Ryo ; Okuzaki, Daisuke ; Motooka, Daisuke ; Shinohara, Masakazu ; Nojima, Satoshi ; Morii, Eiichi

Background : The mechanisms underlying metastasis of colorectal cancer (CRC) remain unclear. C14orf159 is a mitochondrial matrix protein converting d-glutamate to 5-oxo-d-proline. Other metabolic functions of C14orf159, especially on mitochondrial metabolism, and its contribution to CRC metastasis, are not elucidated. Methods : Metabolome analysis by gas chromatography-mass spectrometry, RNA-sequencing analysis, flow cytometry, migration and invasion assay, sphere-formation assay using [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel la protéine adaptatrice FRS2 bêta, exprimée dans un sous-ensemble de cellules épithéliales mammaires et liée à leur membrane, favorise la carcinogenèse du sein en activant le processus inflammatoire via le facteur nucléaire NF-kB

The membrane-linked adaptor FRS2beta fashions a cytokine-rich inflammatory microenvironment that promotes breast cancer carcinogenesis

Takeuchi, Yasuto ; Kimura, Natsuko ; Murayama, Takahiko ; Machida, Yukino ; Iejima, Daisuke ; Nishimura, Tatsunori ; Terashima, Minoru ; Wang, Yuming ; Li, Mengjiao ; Sakamoto, Reiko ; Yamamoto, Mizuki ; Itano, Naoki ; Inoue, Yusuke ; Ito, Masataka ; Yoshida, Nobuaki ; Inoue, Jun-ichiro ; Akashi, Koichi ; Saya, Hideyuki ; Fujita, Koji ; Kuroda, Masahiko ; Kitabayashi, Issay ; Voon, Dominic ; Suzuki, Takeshi ; Tojo, Arinobu ; Gotoh, Noriko

Human breast cancer develops after a long period of latency under premalignant conditions. Strategies to target the premalignant conditions have yet to materialize since the molecular mechanisms remain obscure. Here, we discovered that FRS2β, expressed in a subset of mammary epithelial cells, directly activates nuclear factor–κB (NF-κB) and drives the initiation and promotion of the stroma-rich premalignant conditions. The FRS2β-triggered activation of NF-κB takes place in the early endosomes, [...]

Cet article passe en revue les connaissances concernant l'expression et les fonctions du long ARN non codant NEAT1 des cellules cancéreuses du sein puis analyse le rôle des isoformes NEAT1_1 et NEAT1_2 dans différents sous-types tumoraux

Expression and functions of long non-coding RNA NEAT1 and isoforms in breast cancer

Knutsen, Erik ; Harris, Adrian L. ; Perander, Maria

NEAT1 is a highly abundant nuclear architectural long non-coding RNA. There are two overlapping NEAT1 isoforms, NEAT1_1 and NEAT1_2, of which the latter is an essential scaffold for the assembly of a class of nuclear ribonucleoprotein bodies called paraspeckles. Paraspeckle formation is elevated by a wide variety of cellular stressors and in certain developmental processes, either through transcriptional upregulation of the NEAT1 gene or through a switch from NEAT1_1 to NEAT1_2 isoform [...]

Menée à l'aide de modèles murins de cancer du sein triple négatif, cette étude met en évidence le rôle de la protéine RNF2, une sous-unité du complexe répresseur polycomb 1, dans l'immunité antitumorale liée aux lymphocytes T CD4+ et aux cellules NK

RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T-cell-dependent antitumor immunity

Zhang, Zhuo ; Luo, Lin ; Xing, Chuan ; Chen, Yu ; Xu, Peng ; Li, Mao ; Zeng, Ling ; Li, Chao ; Ghosh, Sadashib ; Della Manna, Deborah ; Townes, Tim ; Britt, William J. ; Wajapeyee, Narendra ; Sleckman, Barry P. ; Chong, Zechen ; Leavenworth, Jianmei Wu ; Yang, Eddy S.

Expanding the utility of immune-based cancer treatments is a clinical challenge due to tumor-intrinsic factors that suppress the immune response. Here we report the identification of tumoral ring finger protein 2 (RNF2), the core subunit of polycomb repressor complex 1, as a negative regulator of antitumor immunity in various human cancers, including breast cancer. In syngeneic murine models of triple-negative breast cancer, we found that deleting genes encoding the polycomb repressor complex 1 [...]

Cet article passe en revue les études concernant les relations entre le microbiome gastro-intestinal et les cancers des voies biliaires, identifie les facteurs de confusion de ces études, examine le rôle potentiel du microbiome dans le diagnostic, le pronostic et le traitement de ces cancers et propose des axes de recherche

Potential influence of the microbiome environment in patients with biliary tract cancer and implications for therapy

Wheatley, Roseanna C. ; Kilgour, Elaine ; Jacobs, Timothy ; Lamarca, Angela ; Hubner, Richard A. ; Valle, Juan W. ; McNamara, Mairéad G.

Biliary tract cancers, including intra- and extra-hepatic cholangiocarcinoma as well as gallbladder cancer, are associated with poor prognosis and the majority of patients present with advanced-stage, non-resectable disease at diagnosis. Biliary tract cancer may develop through an accumulation of genetic and epigenetic alterations and can be influenced by microbial exposure. Furthermore, the liver and biliary tract are exposed to the gastrointestinal microbiome through the gut–liver axis. The [...]