Menée in vitro et in vivo, cette étude met en évidence le rôle joué par l'expression du récepteur RACK1 dans la croissance d'une tumeur hépatique et l'apparition d'une résistance à la chimiothérapie

Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular carcinoma

Ruan, Yuanyuan ; Sun, Linlin ; Hao, Yuqing ; Wang, Lijing ; Xu, Jiejie ; Zhang, Wen ; Xie, Jianhui ; Guo, Liang ; Zhou, Lei ; Yun, Xiaojing ; Zhu, Hongguang ; Shen, Aiguo ; Gu, Jianxin

Coordinated translation initiation is coupled with cell cycle progression and cell growth, whereas excessive ribosome biogenesis and translation initiation often lead to tumor transformation and survival. Hepatocellular carcinoma (HCC) is among the most common and aggressive cancers worldwide and generally displays inherently high resistance to chemotherapeutic drugs. We found that RACK1, the receptor for activated C-kinase 1, was highly expressed in normal liver and frequently upregulated in [...]

Menée in vitro, cette étude montre que deux gènes de récepteurs à activité tyrosine kinase, ATM et MET, sont en interaction synthétique létale avec le suppresseur de tumeurs p53

ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53

Sullivan, Kelly D. ; Padilla-Just, Nuria ; Henry, Ryan E. ; Porter, Christopher C. ; Kim, Jihye ; Tentler, John J. ; Eckhardt, S. Gail ; Tan, Aik Choon ; DeGregori, James ; Espinosa, Joaquín M.

The p53 tumor suppressor orchestrates alternative stress responses including cell cycle arrest and apoptosis, but the mechanisms defining cell fate upon p53 activation are poorly understood. Several small-molecule activators of p53 have been developed, including Nutlin-3, but their therapeutic potential is limited by the fact that they induce reversible cell cycle arrest in most cancer cell types. We report here the results of a genome-wide short hairpin RNA screen for genes that are lethal in [...]

Menée à l'aide de modèles murins, cette étude met en évidence le rôle joué par des récepteurs inhibiteurs de l'activité immunitaire dans la différenciation des cellules leucémiques

Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development

Zheng, Junke ; Umikawa, Masato ; Cui, Changhao ; Li, Jiyuan ; Chen, Xiaoli ; Zhang, Chaozheng ; Hyunh, HoangDinh ; Kang, Xunlei ; Silvany, Robert ; Wan, Xuan ; Ye, Jingxiao ; Canto, Alberto Puig ; Chen, Shu-Hsia ; Wang, Huan-You ; Ward, E. Sally ; Zhang, Cheng Cheng

How environmental cues regulate adult stem cell and cancer cell activity through surface receptors is poorly understood. Angiopoietin-like proteins (ANGPTLs), a family of seven secreted glycoproteins, are known to support the activity of haematopoietic stem cells (HSCs) in vitro and in vivo. ANGPTLs also have important roles in lipid metabolism, angiogenesis and inflammation, but were considered ‘orphan ligands’ because no receptors were identified. Here we show that the immune-inhibitory [...]

Menée in vitro et in vivo, cette étude suggère que, dans les cancers de l'ovaire, le ganglioside GD3 (un glycolipide acide) joue un rôle essentiel dans le mécanisme d'échappement au système immunitaire

Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer

Webb, Tonya J. ; Li, Xiangming ; Giuntoli, Robert L. ; Lopez, Pablo H. H. ; Heuser, Christoph ; Schnaar, Ronald L. ; Tsuji, Moriya ; Kurts, Christian ; Oelke, Mathias ; Schneck, Jonathan P.

Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 [...]

Menée in vitro et in vivo, cette étude met en évidence un mécanisme par lequel la protéine SPRY2, en régulant la voie de signalisation PI3K/AKT, joue un rôle de suppresseur de tumeurs dans le cancer de la prostate

SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis

Gao, Meiling ; Patel, Rachana ; Ahmad, Imran ; Fleming, Janis ; Edwards, Joanne ; McCracken, Stuart ; Sahadevan, Kanagasabai ; Seywright, Morag ; Norman, Jim ; Sansom, Owen ; Leung, Hing Y.

Loss of SPRY2 and activation of receptor tyrosine kinases are common events in prostate cancer (PC). However, the molecular basis of their interaction and clinical impact remains to be fully examined. SPRY2 loss may functionally synergize with aberrant cellular signalling to drive PC and to promote treatment-resistant disease. Here, we report evidence for a positive feedback regulation of the ErbB-PI3K/AKT cascade by SPRY2 loss in in vitro as well as pre-clinical in vivo models and clinical PC. [...]