Menée à partir de données génétiques issues de plusieurs sources (Projet TGCA, AmiGO, ...), cette étude analyse la relation entre la fréquence des mutations au sein d'une même famille d'oncogènes, l'utilisation des codons et l'oncogénicité

Mutation bias within oncogene families is related to proliferation-specific codon usage

Benisty, Hannah ; Weber, Marc ; Hernandez-Alias, Xavier ; Schaefer, Martin H. ; Serrano, Luis

In light of the genetic code, combinations of three nucleotides which are known as synonymous codons, can give rise to the same amino acid. Despite the homology at the protein level, these different codons are recognized distinctly by the translational machinery. The unequal use of synonymous codons influences protein expression. Surprisingly, we find that the coding sequences of KRAS and other frequently mutated cancer genes are adapted to be efficiently translated in proliferating cells in [...]

Menée in vitro et à l'aide d'une xénogreffe d'adénocarcinome du poumon sur un modèle murin, cette étude identifie le gène de fusion CD63–BCAR4 et met en évidence son rôle dans la tumorigenèse et le processus métastatique

A fusion of CD63–BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis

Bae, Kieun ; Kim, Jin Hee ; Jung, Hyojik ; Kong, Sun-Young ; Kim, Yun-Hee ; Kim, Sunshin ; Lee, Geon Kook ; Lee, Jin Soo ; Lee, Jake June-Koo ; Ju, Young Seok ; Choi, Yang-Kyu ; Yoon, Kyong-Ah

Background : Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated. Methods : Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63–BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To [...]

Cet article analyse le mécanisme par lequel une transition épithélio-mésenchymateuse partielle ou transitoire et des modifications des caractéristiques mécaniques du microenvironnement tumoral peuvent favoriser la dissémination de cellules cancéreuses

Metastasis: crosstalk between tissue mechanics and tumour cell plasticity

Coban, Bircan ; Bergonzini, Cecilia ; Zweemer, Annelien J. M. ; Danen, Erik H. J.

Despite the fact that different genetic programmes drive metastasis of solid tumours, the ultimate outcome is the same: tumour cells are empowered to pass a series of physical hurdles to escape the primary tumour and disseminate to other organs. Epithelial-to-mesenchymal transition (EMT) has been proposed to drive the detachment of individual cells from primary tumour masses and facilitate the subsequent establishment of metastases in distant organs. However, this concept has been challenged by [...]

Cet article passe en revue les études concernant l'effet de l'instabilité chromosomique et des mutations génétiques sur la migration et l'invasion des cellules cancéreuses

Mutational drivers of cancer cell migration and invasion

Novikov, Nikita M. ; Zolotaryova, Sofia Y. ; Gautreau, Alexis M. ; Denisov, Evgeny V.

Genomic instability and mutations underlie the hallmarks of cancer—genetic alterations determine cancer cell fate by affecting cell proliferation, apoptosis and immune response, and increasing data show that mutations are involved in metastasis, a crucial event in cancer progression and a life-threatening problem in cancer patients. Invasion is the first step in the metastatic cascade, when tumour cells acquire the ability to move, penetrate into the surrounding tissue and enter lymphatic and [...]

Menée in vitro et à l'aide de modèles murins transgéniques de carcinome corticosurrénalien, cette étude démontre que les gènes HOX favorisent la prolifération cellulaire et qu'ils peuvent constituer des cibles thérapeutiques

HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours

Francis, Jeffrey C. ; Gardiner, Jennifer R. ; Renaud, Yoan ; Chauhan, Ritika ; Weinstein, Yacob ; Gomez-Sanchez, Celso ; Lefrançois-Martinez, Anne-Marie ; Bertherat, Jérôme ; Val, Pierre ; Swain, Amanda

Background : Understanding the pathways that drive adrenocortical carcinoma (ACC) is essential to the development of more effective therapies. This study investigates the role of the transcription factor HOXB9 and other HOX factors in ACC and its treatment. Methods : We used transgenic mouse models to determine the role of Hoxb9 in adrenal tumour development. Patient transcriptomic data was analysed for the expression of HOX genes and their association with disease. Drug response studies on [...]

Cet article analyse le rôle de la phosphorylation oxydative mitochondriale dans l'adaptation des mélanomes cutanés à leur environnement

Mitochondrial oxidative phosphorylation in cutaneous melanoma

Kumar, Prakrit R. ; Moore, Jamie A. ; Bowles, Kristian M. ; Rushworth, Stuart A. ; Moncrieff, Marc D.

The Warburg effect in tumour cells is associated with the upregulation of glycolysis to generate ATP, even under normoxic conditions and the presence of fully functioning mitochondria. However, scientific advances made over the past 15 years have reformed this perspective, demonstrating the importance of oxidative phosphorylation (OXPHOS) as well as glycolysis in malignant cells. The metabolic phenotypes in melanoma display heterogeneic dynamism (metabolic plasticity) between glycolysis and [...]

Menée in vitro et à l'aide d'une xénogreffe de mélanome sur un modèle murin, cette étude met en évidence un mécanisme par lequel la sialyltransférase ST3GAL1, induite par le complexe transcriptionnel SOX2-GLI1, favorise le processus métastatique via le récepteur de la tyrosine kinase AXL

ST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL

Pietrobono, Silvia ; Anichini, Giulia ; Sala, Cesare ; Manetti, Fabrizio ; Almada, Luciana L. ; Pepe, Sara ; Carr, Ryan M. ; Paradise, Brooke D. ; Sarkaria, Jann N. ; Davila, Jaime I. ; Tofani, Lorenzo ; Battisti, Ilaria ; Arrigoni, Giorgio ; Ying, Li ; Zhang, Cheng ; Li, Hu ; Meves, Alexander ; Fernandez-Zapico, Martin E. ; Stecca, Barbara

Understanding the molecular events controlling melanoma progression is of paramount importance for the development of alternative treatment options for this devastating disease. Here we report a mechanism regulated by the oncogenic SOX2-GLI1 transcriptional complex driving melanoma invasion through the induction of the sialyltransferase ST3GAL1. Using in vitro and in vivo studies, we demonstrate that ST3GAL1 drives melanoma metastasis. Silencing of this enzyme suppresses melanoma invasion and [...]

Menée à l'aide de lignées cellulaires de cancer colorectal, d'organoïdes et de xénogreffes dérivées de tumeurs de patients, cette étude met en évidence un mécanisme par lequel RALY, une protéine liant l'ARN, modifie le métabolisme mitochondrial en favorisant la transformation post-transcriptionnelle de microARNs

RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer

Sun, Lei ; Wan, Arabella ; Zhou, Zhuolong ; Chen, Dongshi ; Liang, Heng ; Liu, Chuwei ; Yan, Shijia ; Niu, Yi ; Lin, Ziyou ; Zhan, Siyue ; Wang, Shanfeng ; Bu, Xianzhang ; He, Weiling ; Lu, Xiongbin ; Xu, Anlong ; Wan, Guohui

Objective : Dysregulated cellular metabolism is a distinct hallmark of human colorectal cancer (CRC). However, metabolic programme rewiring during tumour progression has yet to be fully understood. Design : We analysed altered gene signatures during colorectal tumour progression, and used a complex of molecular and metabolic assays to study the regulation of metabolism in CRC cell lines, human patient-derived xenograft mouse models and tumour organoid models. Results : We identified a novel [...]

Cet article analyse le rôle de la cystéine dans le remodelage du métabolisme des cellules cancéreuses ainsi que ses interactions avec d'autres voies métaboliques, puis identifie les stratégies thérapeutiques potentielles permettant de cibler le métabolisme de cet acide aminé

Cysteine metabolic circuitries: druggable targets in cancer

Bonifácio, Vasco D. B. ; Pereira, Sofia A. ; Serpa, Jacinta ; Vicente, João B.

To enable survival in adverse conditions, cancer cells undergo global metabolic adaptations. The amino acid cysteine actively contributes to cancer metabolic remodelling on three different levels: first, in its free form, in redox control, as a component of the antioxidant glutathione or its involvement in protein s-cysteinylation, a reversible post-translational modification; second, as a substrate for the production of hydrogen sulphide (H2S), which feeds the mitochondrial electron transfer [...]

Menée à partir d'échantillons sanguins et d'échantillons tumoraux prélevés sur des patients atteints d'un cancer de la tête et du cou, cette étude analyse les caractéristiques de la réponse des lymphocytes B ciblant le papillomavirus humain

Defining HPV-specific B cell responses in patients with head and neck cancer

Wieland, Andreas ; Patel, Mihir R. ; Cardenas, Maria A. ; Eberhardt, Christiane S. ; Hudson, William H. ; Obeng, Rebecca C. ; Griffith, Christopher C. ; Wang, Xu ; Chen, Zhuo G. ; Kissick, Haydn T. ; Saba, Nabil F. ; Ahmed, Rafi

Tumours often contain B cells and plasma cells but the antigen specificity of these intratumoral B cells is not well understood1–8. Here we show that human papillomavirus (HPV)-specific B cell responses are detectable in samples from patients with HPV-positive head and neck cancers, with active production of HPV-specific IgG antibodies in situ. HPV-specific antibody secreting cells (ASCs) were present in the tumour microenvironment, with minimal bystander recruitment of influenza-specific [...]