A partir de 46 échantillons de biopsies du côlon prélevées sur des patients (avec ou sans rectocolite hémorragique, avec ou sans cancer), cette étude identifie un ensemble de mutations de l'ADN mitochondrial qui favorisent la transformation maligne d'une prénéoplasie chez des patients présentant une rectocolite hémorragique, mais font l'objet d'une sélection négative au cours de la progression tumorale

Mitochondrial DNA mutations are associated with ulcerative colitis preneoplasia but tend to be negatively selected in cancer

Baker, Kathryn T. ; Nachmanson, Daniela ; Kumar, Shilpa ; Emond, Mary J. ; Ussakli, Cigdem ; Brentnall, Teresa A. ; Kennedy, Scott R. ; Risques, Rosa Ana

The role of mitochondrial DNA (mtDNA) mutations in cancer remains controversial. Ulcerative Colitis (UC) is an inflammatory bowel disease that increases the risk of colorectal cancer and involves mitochondrial dysfunction, making it an ideal model to study the role of mtDNA in tumorigenesis. Our goal was to comprehensively characterize mtDNA mutations in UC tumorigenesis using Duplex Sequencing, an ultra-accurate next generation sequencing method. We analyzed 46 colon biopsies from non-UC and [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en présence de mannose, les cellules tumorales accumulent ce monosacharride, ce qui perturbe le métabolisme du glucose, réduit la prolifération cellulaire et accroît la sensibilité aux agents cytotoxiques

Mannose impairs tumour growth and enhances chemotherapy

Gonzalez, Pablo Sierra ; O’Prey, James ; Cardaci, Simone ; Barthet, Valentin J. A. ; Sakamaki, Jun-ichi ; Beaumatin, Florian ; Roseweir, Antonia ; Gay, David M. ; Mackay, Gillian ; Malviya, Gaurav ; Kania, Elżbieta ; Ritchie, Shona ; Baudot, Alice D. ; Zunino, Barbara ; Mrowinska, Agata ; Nixon, Colin ; Ennis, Darren ; Hoyle, Aoisha ; Millan, David ; McNeish, Iain A. ; Sansom, Owen J. ; Edwards, Joanne ; Ryan, Kevin M.

It is now well established that tumours undergo changes in cellular metabolism. As this can reveal tumour cell vulnerabilities and because many tumours exhibit enhanced glucose uptake, we have been interested in how tumour cells respond to different forms of sugar. Here we report that the monosaccharide mannose causes growth retardation in several tumour types in vitro, and enhances cell death in response to major forms of chemotherapy. We then show that these effects also occur in vivo in mice [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, via le recrutement de macrophages, la protéine PAI-1 favorise la tumorigenèse

Plasminogen Activator Inhibitor-1 Promotes the Recruitment and Polarization of Macrophages in Cancer

Kubala, Marta Helena ; Punj, Vasu ; Placencio-Hickok, Veronica Rae ; Fang, Hua ; Fernandez, G. Esteban ; Sposto, Richard ; DeClerck, Yves Albert

Plasminogen activator inhibitor-1 (PAI-1) has a pro-tumorigenic function via its pro-angiogenic and anti-apoptotic activities. Here, we demonstrate that PAI-1 promotes the recruitment and M2 polarization of monocytes/macrophages through different structural domains. Its LRP1 interacting domain regulated macrophage migration, while its C-terminal uPA interacting domain promoted M2 macrophage polarization through activation of p38MAPK and nuclear factor ?B (NF-?B) and induction of an autocrine [...]

Menée à l'aide de xénogreffes, cette étude met en évidence des mécanismes de nature métabolique par lesquels l'enzyme TMPRSS11B favorise la croissance d'une tumeur pulmonaire

Transmembrane Protease TMPRSS11B Promotes Lung Cancer Growth by Enhancing Lactate Export and Glycolytic Metabolism

Updegraff, Barrett L. ; Zhou, Xiaorong ; Guo, Yabin ; Padanad, Mahesh S. ; Chen, Pei-Hsuan ; Yang, Chendong ; Sudderth, Jessica ; Rodriguez-Tirado, Carla ; Girard, Luc ; Minna, John D. ; Mishra, Prashant ; DeBerardinis, Ralph J. ; O’Donnell, Kathryn A.

Pathways underlying metabolic reprogramming in cancer remain incompletely understood. We identify the transmembrane serine protease TMPRSS11B as a gene that promotes transformation of immortalized human bronchial epithelial cells (HBECs). TMPRSS11B is upregulated in human lung squamous cell carcinomas (LSCCs), and high expression is associated with poor survival of non-small cell lung cancer patients. TMPRSS11B inhibition in human LSCCs reduces transformation and tumor growth. Given that [...]

Menée in vitro et in vivo sur des modèles de cancer du sein, cette étude met en évidence des mécanismes par lesquels la protéine EGFL6 favorise l'angiogenèse tumorale et le processus métastatique

EGFL6 promotes breast cancer by simultaneously enhancing cancer cell metastasis and stimulating tumor angiogenesis

An, Jingnan ; Du, Yi ; Fan, Xuejun ; Wang, Yanhong ; Ivan, Cristina ; Zhang, Xue-Guang ; Sood, Anil K. ; An, Zhiqiang ; Zhang, Ningyan

EGFL6, a member of the EGF-like superfamily, plays an important role during embryonic development and has been implicated in promotion of tumor angiogenesis without affecting wound healing. There is very little known about the function of EGFL6 in cancer cells. Here, we investigated whether EGFL6 plays a direct role in cancer cells in addition to the promotion of tumor angiogenesis. Our study showed that EGFL6 promoted epithelial–mesenchymal transition (EMT) and stemness of breast cancer cells [...]

A partir de 69 échantillons tumoraux prélevés sur 11 patients atteints d'un glioblastome, cette étude identifie des populations sous-clonales qui, dotées de capacités infiltrantes, émergent de façon précoce dans la croissance tumorale et sont susceptibles d'induire une récidive de la maladie

Evolutionary dynamics of residual disease in human glioblastoma

Spiteri, I. ; Caravagna, G. ; Cresswell, G. D. ; Vatsiou, A. ; Nichol, D. ; Acar, A. ; Ermini, L. ; Chkhaidze, K. ; Werner, B. ; Mair, R. ; Brognaro, E. ; Verhaak, R. G. W. ; Sanguinetti, G. ; Piccirillo, S. G. M. ; Watts, C. ; Sottoriva, A.

Glioblastoma is the most common and aggressive adult brain malignancy against which conventional surgery and chemoradiation provide limited benefit. Even when a good treatment response is obtained, recurrence inevitably occurs either locally (c.80%) or distally (c.20%), driven by cancer clones that are often genomically distinct from those in the primary tumour. Glioblastoma cells display a characteristic infiltrative phenotype, invading the surrounding tissue and often spreading across the [...]

A partir d'un échantillon aléatoire de 149 articles publiés dans la littérature biomédicale entre 2015 et 2017, cette étude analyse les pratiques de publication en matière de déclaration de conflits d'intérêts et d'accès aux données permettant de répliquer les travaux décrits

Reproducible research practices, transparency, and open access data in the biomedical literature, 2015–2017

Wallach, Joshua D. ; Boyack, Kevin W. ; Ioannidis, John P. A.

Currently, there is a growing interest in ensuring the transparency and reproducibility of the published scientific literature. According to a previous evaluation of 441 biomedical journals articles published in 2000–2014, the biomedical literature largely lacked transparency in important dimensions. Here, we surveyed a random sample of 149 biomedical articles published between 2015 and 2017 and determined the proportion reporting sources of public and/or private funding and conflicts of [...]