News & Comment

A recent paper in Nature shows that tumor exosomes expressing unique integrins can determine organotropic metastasis by preparing pre-metastatic niche through their integrins-mediated fusion with and fertilization of organ-specific resident cells.

Classical inflammatory monocytes and their derivative macrophages promote tumor metastasis whereas CD8⁺ T and NK cells restrict tumor growth. In a recent paper published in Science, Hanna and colleagues demonstrate that another monocyte population, nonclassical patrolling monocytes, is enriched in the microvasculature of tumor-challenged lung and reduces tumor metastasis by recruiting NK cells.

Liquid biopsy is ideal for early diagnosis of cancer and for prognosis upon treatment. Wen et al. describe a methylated CpG tandems amplification and sequencing method to profile hypermethylated CpG islands genome-widely in cell-free DNA, and further identify high performance markers in blood for potential detection of early stage hepatocellular carcinoma.

Adding to the Histone Code at DNA double-strand breaks, Mailand and colleagues now uncover non-degradative ubiquitin marks on linker histone H1 as key signaling intermediates in the DNA damage signal transduction cascade.

A paper recently published in Science reports that adenosine deaminase acting on RNA 1-dependent adenosine-to-inosine editing marks endogenous double strand RNA as self and prevents their immune recognition by cytosolic RNA sensor MDA5.

Inflammasomes control host cell death and inflammation in response to sterile or infectious stimuli. Two recent reports published in Science reveal the structural basis for the assembly of NAIP-NLRC4 inflammasomes.

The mammalian target of rapamycin (mTOR), a protein kinase, is the centre of huge attention due to its importance in intracellular signaling and in health and disease. In their recent study, Yin et al. show that mTOR can regulate signaling through the insulin-like growth factor 1 receptor and that it possesses a new enzymatic activity — the ability to phosphorylate proteins on tyrosine residues.

Chimeric antigen receptors (CARs) are synthetic receptors capable of directing potent antigen-specific anti-tumor T cell responses. A recent report by Wu et al. extends a series of strategies aiming to curb excessive T cell activity, utilizing in this instance a chemical dimerizer to aggregate antigen-binding, T cell-activating and costimulatory domains.

BET inhibition has emerged as a promising epigenetic therapy for malignancies in the last five years, but little consensus has developed regarding what may mediate the axis between sensitivity and resistance. Two recent papers published in Nature attempt to address this question in acute myeloid leukemia (AML) and independently identify the Wnt signaling pathway as a driver and biomarker of therapeutic resistance.

In a surprising twist, a hitherto unrecognized cleavage of the amyloid precursor protein (APP) by η-secretase, followed by α- or β-secretase cleavage releases a novel APP proteolytic fragment, Aη, which causes synaptic injury.

Inflammatory caspases drive a lytic form of cell death called pyroptosis in response to microbial infection and endogenous damage-associated signals. Two studies now demonstrate that cleavage of the substrate gasdermin D by inflammatory caspases necessitates eventual pyroptotic demise of a cell.

To maintain homeostasis, organs replace cells lost through normal cellular turnover, often through the straightforward replication of existing cells. A recent paper in Nature shows that cells in the liver are not equivalent when it comes to their replicative capacity; rather, a subset of hepatocytes defined by the maintenance of active Wnt signaling bears the brunt of responsibility for maintaining liver mass.