Menée à partir d'échantillons tumoraux prélevés sur des patients atteints d'un cancer primitif du côlon, cette étude met en évidence un mécanisme par lequel la protéine SUN2 supprime le développement de métastases

Downregulation of SUN2 promotes metastasis of colon cancer by activating BDNF/TrkB signalling by interacting with SIRT1

Liu, Lijuan ; Li, Si-Wei ; Yuan, Wenxing ; Tang, Jianjun ; Sang, Yi

Distant metastasis is the major cause of colon cancer treatment failure. SAD1/UNC84 domain protein‐2 (SUN2) is a key component of LINC (linker of the nucleoskeleton and cytoskeleton) complexes that may be relevant for metastasis in several cancers. Here, we first confirmed that SUN2 levels were significantly lower in primary colon cancer tissues and distant metastasis than in normal colon tissues, and high SUN2 expression predicted good overall survival (OS). Overexpression of SUN2 or knockdown [...]

Menée notamment à l'aide d'un modèle murin de cancer du côlon, cette étude met en évidence le rôle de la signalisation de l'interleukine IL-11 dans la suppression de la réponse anti-tumorale induite par les lymphocytes T CD4+

Host IL-11 signaling suppresses CD4+ T cell-mediated anti-tumor responses to colon cancer in mice

Huynh, Jennifer ; Baloyan, David ; Chisanga, David ; Shi, Wei ; Brien, Megan ; Afshar-Sterle, Shoukat ; Alorro, Mariah ; Pang, Lokman ; Williams, David S. ; Parslow, Adam C. ; Thilakasiri, Pathum ; Eissmann, Moritz F. ; Boon, Louis ; Masson, Frederick ; Chand, Ashwini L. ; Ernst, Matthias

Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and signals through its cognate receptor subunits, IL11RA and glycoprotein 130 (GP130) to elicit biological responses via the JAK/STAT signaling pathway. IL-11 contributes to cancer progression by promoting the survival and proliferation of cancer cells, but the potential immunomodulatory properties of IL-11 signaling during tumor development have thus far remained unexplored. Here, we have characterized a role for IL-11 in [...]

Menée in vitro et à l'aide de deux modèles murins de tumeur, cette étude met en évidence un mécanisme par lequel le stress chronique induit par les récepteurs adrénergiques favorise le dysfonctionnement du métabolisme des lymphocytes T intratumoraux et le phénomène d'épuisement lymphocytaire

Chronic Adrenergic Stress Contributes to Metabolic Dysfunction and an Exhausted Phenotype in T Cells in the Tumor Microenvironment

Qiao, Guanxi ; Chen, Minhui ; Mohammadpour, Hemn ; MacDonald, Cameron R. ; Bucsek, Mark J. ; Hylander, Bonnie L. ; Barbi, Joseph J. ; Repasky, Elizabeth A.

Metabolic dysfunction and exhaustion in tumor-infiltrating T cells have been linked to ineffectual antitumor immunity and the failure of immune checkpoint inhibitor therapy. We report here that chronic stress plays a previously unrecognized role in regulating the state of T cells in the tumor microenvironment (TME). Using two mouse tumor models, we found that blocking chronic adrenergic stress signaling using the pan β-blocker propranolol or by using mice lacking the β2-adrenergic receptor [...]

Menée à l'aide de cellules fibroblastiques et de lignées cellulaires de cancer du sein, cette étude met en évidence un mécanisme par lequel la tubulation de la membrane cellulaire induite par les phospholipides PI(3,4)P2 favorise le trafic des intégrines et la migration invasive des cellules

PI(3,4)P2-mediated membrane tubulation promotes integrin trafficking and invasive cell migration

Feng, Zhen ; Yu, Cheng-han

The dynamic distribution of phosphoinositide lipids orchestrates intracellular compartmentalization and protein sorting. Here, we report the PI(3,4)P2-dependent endocytosis of adhesion receptor integrin-beta3 at the invadopodium and its implication in promoting invasive cell migration. PI(3,4)P2-rich compartment in the plasma membrane contains integrin-beta3 and is actively internalized through SNX9-mediated membrane invagination as well as dynein-mediated membrane tubulation along cortical [...]

Menée in vitro et à l'aide de modèles murins, cette étude analyse le rôle de différentes sous-populations de fibroblastes associés au cancer dans la croissance d'un cholangiocarcinome

Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations

Affò, Silvia ; Nair, Ajay ; Brundu, Francesco ; Ravichandra, Aashreya ; Bhattacharjee, Sonakshi ; Matsuda, Michitaka ; Chin, LiKang ; Filliol, Aveline ; Wen, Wen ; Song, Xinhua ; Decker, Aubrianna ; Worley, Jeremy ; Caviglia, Jorge Matias ; Yu, Lexing ; Yin, Deqi ; Saito, Yoshinobu ; Savage, Thomas ; Wells, Rebecca G. ; Mack, Matthias ; Zender, Lars ; Arpaia, Nicholas ; Remotti, Helen E. ; Rabadan, Raul ; Sims, Peter ; Leblond, Anne-Laure ; Weber, Achim ; Riener, Marc-Oliver ; Stockwell, Brent R. ; Gaublomme, Jellert ; Llovet, Josep M. ; Michalopoulos, George K. ; Seki, Ekihiro ; Sia, Daniela ; Chen, Xin ; Califano, Andrea ; Schwabe, Robert F.

Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by [...]

Cet article présente un protocole de séquençage de l'ADN permettant de détecter à l'échelle d'une seule cellule des mutations somatiques dans divers échantillons tissulaires

Somatic mutation landscapes at single-molecule resolution

Abascal, Federico ; Harvey, Luke M. R. ; Mitchell, Emily ; Lawson, Andrew R. J. ; Lensing, Stefanie V. ; Ellis, Peter ; Russell, Andrew J. C. ; Alcantara, Raul E. ; Baez-Ortega, Adrian ; Wang, Yichen ; Kwa, Eugene Jing ; Lee-Six, Henry ; Cagan, Alex ; Coorens, Tim H. H. ; Chapman, Michael Spencer ; Olafsson, Sigurgeir ; Leonard, Steven ; Jones, David ; Machado, Heather E. ; Davies, Megan ; Øbro, Nina F. ; Mahubani, Krishnaa T. ; Allinson, Kieren ; Gerstung, Moritz ; Saeb-Parsy, Kourosh ; Kent, David G. ; Laurenti, Elisa ; Stratton, Michael R. ; Rahbari, Raheleh ; Campbell, Peter J. ; Osborne, Robert J. ; Martincorena, Inigo

Somatic mutations drive the development of cancer and may contribute to ageing and other diseases1,2. Despite their importance, the difficulty of detecting mutations that are only present in single cells or small clones has limited our knowledge of somatic mutagenesis to a minority of tissues. Here, to overcome these limitations, we developed nanorate sequencing (NanoSeq), a duplex sequencing protocol with error rates of less than five errors per billion base pairs in single DNA molecules from [...]

Menée à l'aide de lignées cellulaires et de modèles murins, cette étude met en évidence un mécanisme par lequel les neutrophiles associés à la tumeur favorisent le recrutement des lymphocytes B et la différenciation de ces derniers en plasmocytes

Tumor-associated neutrophils drive B-cell recruitment and their differentiation to plasma cells

Shaul, Merav E. ; Zlotnik, Asaf ; Tidhar, Einat ; Schwartz, Asaf ; Arpinati, Ludovica ; Kaisar-Iluz, Naomi ; Mahroum, Sojod ; Mishalian, Inbal ; Fridlender, Zvi G.

A major mechanism through which neutrophils have been suggested to modulate tumor progression involves the interaction and subsequent modulation of other infiltrating immune cells. B cells have been found to infiltrate various cancer types and play a role in tumor immunity, offering new immunotherapy opportunities. Nevertheless, the specific impact of tumor-associated neutrophils (TANs) on B cells has largely been overlooked. In the current study, we aimed to characterize TANs' role in the [...]

Cet article passe en revue les études concernant les interactions cellulaires, via les ARNs des vésicules extracellulaires, dans le microenvironnement des tumeurs mammaires

Breast Cancer Microenvironment Cross Talk through Extracellular Vesicle RNAs

Dogra, Samrita ; Hannafon, Bethany N.

Exploration of extracellular communication has been at the forefront of research efforts in recent years. However, the mechanisms of cell-to-cell communication in complex tissues are poorly understood. What is clear is that cells do not exist in isolation, that they are constantly interacting and communicating with cells in the immediate vicinity and with cells at a distance. Intercellular communication by the release of small extracellular vesicles, called exosomes, loaded with RNAs is one [...]