Menée in vitro et à l'aide de modèles murins de cancer intestinal, cette étude met en évidence un mécanisme par lequel le microbiome intestinal peut abolir l'effet "suppresseur de tumeur" des protéines p53 mutées et rendre ces dernières oncogènes

The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic

Kadosh, Eliran ; Snir-Alkalay, Irit ; Venkatachalam, Avanthika ; May, Shahaf ; Lasry, Audrey ; Elyada, Ela ; Zinger, Adar ; Shaham, Maya ; Vaalani, Gitit ; Mernberger, Marco ; Stiewe, Thorsten ; Pikarsky, Eli ; Oren, Moshe ; Ben-Neriah, Yinon

Somatic mutations in p53, which inactivate the tumour-suppressor function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer1,2. Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encodes p53 in mice) in mouse models of WNT-driven intestinal cancer caused by Csnk1a1 deletion3,4 or ApcMin mutation5. Cancer in these models is known to be facilitated by loss of p533,6. We found that mutant versions of p53 had contrasting [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel la protéine "Sonic hedgehog", en accélérant la réplication de l'ADN, cause un stress de réplication qui favorise le développement d'un médulloblastome

Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma

Tamayo-Orrego, Lukas ; Gallo, David ; Racicot, Frédéric ; Bemmo, Amandine ; Mohan, Sushmetha ; Ho, Brandon ; Salameh, Samer ; Hoang, Trang ; Jackson, Andrew P. ; Brown, Grant W. ; Charron, Frédéric

The mechanisms generating cancer-initiating mutations are not well understood. Sonic hedgehog (SHH) pathway activation is frequent in medulloblastoma (MB), with PTCH1 mutations being a common initiating event. Here we investigated the role of the developmental mitogen SHH in initiating carcinogenesis in the cells of origin: granule cell progenitors (GCPs). We delineate a molecular mechanism for tumor initiation in MB. Exposure of GCPs to Shh causes a distinct form of DNA replication stress, [...]

Menée à l'aide de lignées cellulaires de cancer du poumon non à petites cellules et d'une xénogreffe sur un modèle murin, cette étude met en évidence un mécanisme par lequel le canal cationique TRPM7 et la O-GlcNAcylation favorisent la motilité des cellules cancéreuses et le processus métastatique en stabilisant la protéine c-Myc et la cavéoline-1

A novel TRPM7/O-GlcNAc axis mediates tumour cell motility and metastasis by stabilising c-Myc and caveolin-1 in lung carcinoma

Luanpitpong, Sudjit ; Rodboon, Napachai ; Samart, Parinya ; Vinayanuwattikun, Chanida ; Klamkhlai, Siwaporn ; Chanvorachote, Pithi ; Rojanasakul, Yon ; Issaragrisil, Surapol

Background : Calcium is an essential signal transduction element that has been associated with aggressive behaviours in several cancers. Cell motility is a prerequisite for metastasis, the major cause of lung cancer death, yet its association with calcium signalling and underlying regulatory axis remains an unexplored area. Methods : Bioinformatics database analyses were employed to assess correlations between calcium influx channels and clinical outcomes in non-small cell lung cancer (NSCLC). [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel la bactérie Fusobacterium nucleatum, en se liant aux cellules des tumeurs colorectales et en les envahissant, favorise la migration des cellules cancéreuses via la sécrétion de l'interleukine IL-8 et du ligand CXCL1

Fusobacterium nucleatum host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration

Casasanta, Michael A. ; Yoo, Christopher C. ; Udayasuryan, Barath ; Sanders, Blake E. ; Umaña, Ariana ; Zhang, Yao ; Peng, Huaiyao ; Duncan, Alison J. ; Wang, Yueying ; Li, Liwu ; Verbridge, Scott S. ; Slade, Daniel J.

Bacterial dysbiosis in the gut, particularly an increase in Fusobacterium nucleatum, is associated with colorectal cancer (CRC). Casasanta et al. found that CRC cell–resident F. nucleatum promotes proinflammatory cytokine secretion that stimulates tumor cell migration and invasion. Gene deletion revealed that F. nucleatum infection of HCT116 CRC cells required a membrane adhesin protein that did not mediate bacterial infection of immune cells. Infected CRC cells secreted the cytokines IL-8 and [...]

Menée in vitro et in silico, cette étude met en évidence un mécanisme par lequel la protéine PGRMC1, en altérant le phosphoprotéome et en augmentant la signalisation du récepteur EGFR et des kinases AKT et PI3K, favorise la croissance des tumeurs mammaires

Progesterone receptor membrane component 1 promotes the growth of breast cancers by altering the phosphoproteome and augmenting EGFR/PI3K/AKT signalling

Pedroza, Diego A. ; Rajamanickam, Venkatesh ; Subramani, Ramadevi ; Bencomo, Alejandra ; Galvez, Adriana ; Lakshmanaswamy, Rajkumar

Background : Increased expression of the progesterone receptor membrane component 1 (PGRMC1) has been linked to multiple cancers, including breast cancer. Despite being a regulatory receptor and a potential therapeutic target, the oncogenic potential of PGRMC1 has not been studied. Methods : The impact of PGRMC1 on breast cancer growth and progression was studied following chemical inhibition and alteration of PGRMC1 expression, and evaluated by using online-based gene expression datasets of [...]

Menée à l'aide de lignées cellulaires de carcinome épidermoïde de la cavité buccale, d'échantillons tumoraux et d'une xénogreffe sur un modèle murin, cette étude met en évidence le mécanisme par lequel la glucose-6-phosphate déshydrogénase régule la transition épithélio-mésenchymateuse et le processus métastatique

Suppression of G6PD induces the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin to block epithelial-mesenchymal transition and lymphatic metastasis

Wang, Yifei ; Li, Qingxiang ; Niu, Lixuan ; Xu, Le ; Guo, Yuxing ; Wang, Lin ; Guo, Chuanbin

Background : As the rate-limit enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) plays important roles in tumour progression, but the exact mechanism through which G6PD controls cancer metastasis remains unclear. Methods : G6PD expression in resected oral squamous cell carcinoma (OSCC) samples was analysed by immunohistochemistry. The effects and mechanism of G6PD suppression on OSCC cell lines were measured by transwell assay, wound healing assay, western and [...]

Cet article présente les mécanismes de signalisation du facteur TGFbêta dans les tumeurs et leur microenvironnement puis analyse les différentes approches pour inhiber ces mécanismes

TGFbêta biology in cancer progression and immunotherapy

Derynck, Rik ; Turley, Shannon J. ; Akhurst, Rosemary J.

TGFβ signalling has key roles in cancer progression: most carcinoma cells have inactivated their epithelial antiproliferative response and benefit from increased TGFβ expression and autocrine TGFβ signalling through effects on gene expression, release of immunosuppressive cytokines and epithelial plasticity. As a result, TGFβ enables cancer cell invasion and dissemination, stem cell properties and therapeutic resistance. TGFβ released by cancer cells, stromal fibroblasts and other cells in the [...]

Cet article analyse le rôle des organoïdes dans la recherche sur le cancer

Current concepts in tumour-derived organoids

Porter, Ross J. ; Murray, Graeme I. ; McLean, Mairi H.

Cancer comprises a collection of highly proliferative and heterogeneous cells growing within an adaptive and evolving tumour microenvironment. Cancer survival rates have significantly improved following decades of cancer research. However, many experimental and preclinical studies do not translate to the bedside, reflecting the challenges of modelling the complexities and multicellular basis of human disease. Organoids are novel, complex, three-dimensional ex vivo tissue cultures that are [...]