Menée à l'aide de lignées cellulaires de carcinome hépatocellulaire, de tissus tumoraux et de modèles murins, cette étude met en évidence un mécanisme par lequel la rigidité de la matrice extracellulaire, via l'augmentation de l'expression de l'histone acétyltransférase KAT6A et du facteur de transcription SOX2, favorise la progression tumorale

Matrix stiffness-induced upregulation of histone acetyltransferase KAT6A promotes hepatocellular carcinoma progression through regulating SOX2 expression

Zhao, Wei ; Mo, Huanye ; Liu, Runkun ; Chen, Tianxiang ; Yang, Nan ; Liu, Zhikui

Background : Lysine acetyltransferase 6 A (KAT6A) is a MYST-type histone acetyltransferase (HAT) enzyme, which contributes to histone modification and cancer development. However, its biological functions and molecular mechanisms, which respect to hepatocellular carcinoma (HCC), are still largely unknown. Methods : Immunohistochemical, western blot and qRT-PCR analysis of KAT6A were performed. A series of in vitro and in vivo experiments were conducted to reveal the role of KAT6A in the [...]

Menée in vitro et à l'aide d'un modèle murin de mélanome, cette étude met en évidence un mécanisme par lequel les cellules cancéreuses récupèrent les mitochondries des cellules souches dérivées de la moelle osseuse après avoir stimulé la biogenèse mitochondriale de ces cellules via la surexpression du co-activateur transcriptionnel PGC-1 alpha

PGC-1 alpha induced mitochondrial biogenesis in stromal cells underpins mitochondrial transfer to melanoma

Kumar, Prakrit R. ; Saad, Mona ; Hellmich, Charlotte ; Mistry, Jayna J. ; Moore, Jamie A. ; Conway, Shannon ; Morris, Christopher J. ; Bowles, Kristian M. ; Moncrieff, Marc D. ; Rushworth, Stuart A.

Introduction : Progress in the knowledge of metabolic interactions between cancer and its microenvironment is ongoing and may lead to novel therapeutic approaches. Until recently, melanoma was considered a glycolytic tumour due to mutations in mitochondrial-DNA, however, these malignant cells can regain OXPHOS capacity via the transfer of mitochondrial-DNA, a process that supports their proliferation in-vitro and in-vivo. Here we study how melanoma cells acquire mitochondria and how this [...]

Menée in vitro, in silico et à l'aide d'un modèle murin, cette étude met en évidence le rôle de la protéine interagissant avec le récepteur AhR (Aryl-hydrocarbon receptor) dans la régulation des propriétés tumorigènes et métastatiques des cellules colorectales cancéreuses

Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis

Solís-Fernández, Guillermo ; Montero-Calle, Ana ; Sánchez-Martínez, Maricruz ; Peláez-García, Alberto ; Fernández-Aceñero, María Jesús ; Pallarés, Pilar ; Alonso-Navarro, Miren ; Mendiola, Marta ; Hendrix, Jelle ; Hardisson, David ; Bartolomé, Ruben A. ; Hofkens, Johan ; Rocha, Susana ; Barderas, Rodrigo

Background : Liver metastasis is the primary cause of colorectal cancer (CRC)-associated death. Aryl-hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl-hydrocarbon receptor-mediated signalling, is overexpressed in highly metastatic human KM12SM CRC cells and other highly metastatic CRC cells. Methods : Meta-analysis and immunohistochemistry were used to assess the relevance of AIP. Cellular functions and signalling mechanisms mediated by AIP were assessed [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel la voie de signalisation de la cyclooxygénase 2 et de la prostaglandine E2 favorise l'échappement immunitaire des adénomes colorectaux

The COX-2–PGE2 Pathway Promotes Tumor Evasion in Colorectal Adenomas

Wei, Jie ; Zhang, Jinyu ; Wang, Dingzhi ; Cen, Bo ; Lang, Jessica D. ; DuBois, Raymond N.

The mechanisms underlying the regulation of a checkpoint receptor, PD-1, in tumor-infiltrating immune cells during the development of colorectal cancer are not fully understood. Here we demonstrate that COX-2–derived PGE2, an inflammatory mediator and tumor promoter, induces PD-1 expression by enhancing NFκB's binding to the PD-1 promoter via an EP4–PI3K–Akt signaling pathway in both CD8+ T cells and macrophages. Moreover, PGE2 suppresses CD8+ T-cell proliferation and cytotoxicity against tumor [...]

Cet article passe en revue les études concernant le rôle de l'épissage alternatif de l'ARN dans les cancers pédiatriques, décrit plusieurs variants d'épissage, présente leurs effets sur la formation de néoantigènes et la chimiorésistance puis identifie des stratégies thérapeutiques reposant sur la modification de l'épissage

Alternative RNA Splicing Defects in Pediatric Cancers: New Insights in Tumorigenesis and Potential Therapeutic Vulnerabilities

Venkataramany, A. S. ; Schieffer, K. M. ; Lee, K. ; Cottrell, C. E. ; Wang, P. Y. ; Mardis, E. R. ; Cripe, T. P. ; Chandler, D. S.

Background : Compared to adult cancers, pediatric cancers are uniquely characterized by a genomically stable landscape and lower tumor mutational burden. However, alternative splicing, a global cellular process that produces different mRNA/protein isoforms from a single mRNA transcript, has been increasingly implicated in the development of pediatric cancers. Design : We review the current literature on the role of alternative splicing in adult cancer, cancer predisposition syndromes, and [...]