May 10, 2017
Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer
J. S. Lim, A. Ibaseta, M. M. Fischer, B. Cancilla, G. O’Young, S. Cristea, V. C. Luca, D. Yang, N. S. Jahchan, C. Hamard, M. Antoine, M. Wislez, C. Kong, J. Cain, Y.-W. Liu, A. M. Kapoun, K. C. Garcia, T. Hoey, C. L. Murriel, J. Sage , nature , DOI: 10.1038/nature22323
The Notch signalling pathway mediates cell fate decisions and is tumour suppressive or oncogenic depending on the context. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung cancer, loss-of-function mutations in NOTCH genes and the...
May 9, 2017
Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using CRISPR/Cas9
R. Torres-Ruiz , M. Martinez-Lage , M. C. Martin , A. Garcia , C. Bueno , J. Castaño , J. C. Ramirez , P. Menendez , J. C. Cigudosa , S. Rodriguez-Perales , Stem Cell Reports , DOI: 10.1016/j.stemcr.2017.04.014
Efficient methodologies for recreating cancer-associated chromosome translocations are in high demand as tools for investigating how such events initiate cancer. The CRISPR/Cas9 system has been used to reconstruct the genetics of these complex rearrangements at native loci while maintaining the architecture and regulatory elements. However, the CRISPR system remains inefficient...
May 8, 2017
FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients
R. A. Tassi, P. Todeschini, E. R. Siegel, S. Calza, P. Cappella, L. Ardighieri, M. Cadei, M. Bugatti, C. Romani, E. Bandiera, L. Zanotti, L. Tassone, D. Guarino, C. Santonocito, E. D. Capoluongo, L. Beltrame, E. Erba, S. Marchini, M. D’Incalci, C. Donzelli, A. D. Santin, S. Pecorelli, E. Sartori, E. Bignotti, F. Odicino, A. Ravaggi , Journal of Experimental & Clinical Cancer Research , DOI: 10.1186/s13046-017-0536-y
Background: Epithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis...
May 2, 2017
Inhibition of pH regulation as a therapeutic strategy in hypoxic human breast cancer cells
J. Meehan, C. Ward, A. Turnbull, J. Bukowski-Wills, A. J. Finch, E. J. Jarman, C. Xintaropoulou, C. Martinez-Perez, M. Gray, M. Pearson, P. Mullen, C. T. Supuran, F. Carta, D. J. Harrison, I. H. Kunkler, S. P. Langdon , Oncotarget , doi: 10.18632/oncotarget.17143
Hypoxic cancer cells exhibit resistance to many therapies. This study compared the therapeutic effect of targeting the pH regulatory proteins (CAIX, NHE1 and V-ATPase) that permit cancer cells to adapt to hypoxic conditions, using both 2D and 3D culture models. Drugs targeting CAIX, NHE1 and V-ATPase exhibited anti-proliferative effects in...
May 2, 2017
In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias
S. Muñoz, S. Búa, S. Rodríguez-Acebes, D. Megías, S. Ortega, A. de Martino, J. Méndez , Cell Reports , DOI: 10.1016/j.celrep.2017.04.032
Mammalian DNA replication origins are “licensed” by the loading of DNA helicases, a reaction that is mediated by CDC6 and CDT1 proteins. After initiation of DNA synthesis, CDC6 and CDT1 are inhibited to prevent origin reactivation and DNA overreplication before cell division. CDC6 and CDT1 are highly expressed in many...