Feb 14, 2018
Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas
I. Cobo, P. Martinelli, M. Flández, L. Bakiri, M. Zhang, E. Carrillo-de-Santa-Pau, J. Jia, V. J. Sánchez-Arévalo Lobo, D. Megías, I. Felipe, N. del Pozo, I. Millán, L. Thommesen, T. Bruland, S. H. Olson, J. Smith, K. Schoonjans, W. R. Bamlet, G. M. Petersen, N. Malats, L. T. Amundadottir, E. F. Wagner, F. X. Real , nature , DOI: 10.1038/nature25751
Chronic inflammation increases the risk of developing one of several types of cancer. Inflammatory responses are currently thought to be controlled by mechanisms that rely on transcriptional networks that are distinct from those involved in cell differentiation1,2,3. The orphan nuclear receptor NR5A2 participates in a wide variety of processes, including...
Feb 14, 2018
Spatial Aspects of Oncogenic Signaling Determine Response to Combination Therapy in Slice Explants from Kras-driven Lung Tumors
K. Närhi, A. S. Nagaraj, E. Parri, R. Turkki, P.W. van Duijn, A. Hemmes, J. Lahtela, V. Uotinen, M. I. Märänpää, K. Salmenkivi, J. Räsänen, N. Linder, J. Trapman, A. Rannikko, O. Kallioniemi, T. af Hällström, J. Lundin, W. Sommergruber, S. Anders, E.W. Verschuren , The Journal of Pathology , DOI: 10.1002/path.5059
A key question in precision medicine is how functional heterogeneity in solid tumors informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signaling and therapy response can be modeled in precision-cut slices from Kras-driven non-small cell lung cancer (NSCLC) of varying histopathologies. Unexpectedly, profiling of in situ tumors demonstrates...
Feb 13, 2018
Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers
O. M.T. Pearce, R. M. Delaine-Smith, E. Maniati, S. Nichols, J. Wang, S. Böhm, V. Rajeeve, D. Ullah, P. Chakravarty, R. R. Jones, A. Montfort, T. Dowe, J. Gribben, J. L. Jones, H. M. Kocher, J. S. Serody, B. G. Vincent, J. Connelly, J. D. Brenton, C. Chelala, P. R. Cutillas, M. Lockley, C. Bessant, M. M. Knight, F. R. Balkwill , Cancer Discovery , DOI: 10.1158/2159-8290.CD-17-0284
We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we...
Feb 10, 2018
The prognostic significance of PDL1 expression in locally advanced non-small-cell lung cancer (LA-NSCLC) treated with definitive intent.
D. Mitra, V. Agarwal, Y.-H. Chen, E. H. Baldini, D. A. Barbie, A. B. Chen , Journal of Clinical Oncology , DOI: 10.1200/JCO.2018.36.5_suppl.150
Background: The PACIFIC trial showed an 11-month (mo) improved median (med) progression-free survival after definitive chemoradiation in LA-NSCLC using the PDL1 inhibitor, durvalumab. This study will likely change practice and puts further emphasis on understanding the significance of immune marker expression in this poor-prognosis disease. Methods: From 1999-2012, pathology specimens...
Feb 9, 2018
The IAP family member BRUCE regulates autophagosome–lysosome fusion
P. Ebner, I. Poetsch, L. Deszcz, T. Hoffmann, J. Zuber, F. Ikeda , nature communications , DOI:10.1038/s41467-018-02823-x
Autophagy has an important role in cellular homeostasis by degrading and recycling cytotoxic components. Ubiquitination is known to target cargoes for autophagy; however, key components of this pathway remain elusive. Here we performed an RNAi screen to uncover ubiquitin modifiers that are required for starvation-induced macroautophagy in mammalian cells. Our...