Using a novel strain of influenza A and a modified melanoma model system, work by Chiara Pirillo, Ed Roberts and colleagues, published in ScienceImmunology, has shown that co-encoded contextual information and antigen allow resident conventional dendritic cells (rDCs) to be appropriately activated in the lymph node. By determining how immune responses may be improved by elevated rDC function, these findings have important implications on the design of cancer vaccines and immunotherapies.
Recent work by Tom MacVicar and colleagues has revealed that the kinase NME6 drives mitochondrial gene expression. The researchers demonstrated that NME6 supplies pyrimidine ribonucleotides for mitochondrial transcription and ensures accumulation of mitochondrial transcripts and respiratory complexes. Additionally, loss of NME6 or its kinase activity impairs mitochondrial gene expression and OXPHOS function. This research highlights the importance of mitochondrial ribonucleotide metabolism for healthy mitochondrial function. [Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression]
Johan Vande Voorde and the Cancer Grand Challenges Rosetta team have published a paper in Nature Metabolism that used genetically engineered mouse models and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of colorectal cancer on the metabolic landscape of the intestine. Their work revealed that loss of the gene APC in the mouse intestine drives expression of the enzyme adenosylhomocysteinase (AHCY) which is transcriptionally upregulated in human colorectal cancer. This work highlights (AHCY) as a potential drug target for the second most common cause of cancer-related deaths worldwide.
David Bryant and colleagues have published a study in The EMBO Journal identifying ARF6 as a therapeutic vulnerability in PTEN-depleted high-grade serous ovarian carcinoma. PTEN depletion leads to PIP3-rich invasive membrane protrusions into the extracellular matrix and ARF6 was found to be essential to this process. The expression of an ARF6 module (CYTH2-ARF6-AGAP1) was shown to be inversely associated with patient outcome, allowing for the prediction of clinical outcomes in ovarian cancer patients.
In their recent article in Nature Communications, Gareth Inman’s lab provides a comprehensive overview of the molecular drivers and events that promote cutaneous squamous cell carcinoma (cSCC) disease progression from UV-induced precancerous actinic keratosis to malignant invasive cSCC and metastasis. The researchers performed cross-species experiments to reveal that the disease progresses in a continuum from a differentiated to a progenitor-like state. Knowing the events that promote and accompany disease progression provides potential therapeutic targets for cSCC.
