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Loss of LIFRSTAT3 signalling in metastatic breast cancer cells reduces expression of dormancy-related genes and promotes bone marrow colonization and osteoclastogenesis.p1078
Lysosomes are digestive organelles of the endocytic and autophagic pathways. Increasing lysosome enzyme activities could help to clear pathological cellular waste. A recent study shows that lysosomal digestive functions can be promoted in isolated cells and mice by pharmacologically stimulating the autophagy- and lysosome-regulating transcription factors TFEB and ZKSCAN3 through previously unrecognized mTORC1-independent pathways acting via PKC.
Limited perfusion of solid tumours produces a nutrient-deprived tumour core microenvironment. Low glutamine levels in the tumour core are now shown to lead to reduced levels of α-ketoglutarate and decreased histone demethylase activity, thereby promoting a less differentiated and more therapy-resistant state of the tumour cells.
Kodo et al. show that patient-specific iPSC-derived cardiomyocytes recapitulate the proliferative defects associated with the disease, which are a result of TBX20 mutations and abnormal TGF-β signalling.
Using a chimaeric integrin α5 (where the tail is replaced by that of α2), Yun et al. show that in endothelial cells, integrin α5 interacts with the cAMP-specific phosphodiesterase PDE4D5 to reduce cAMP levels and inflammation both in vitro and in vivo.
Microtubules can self-repair in vitro in response to stress. Théry and colleagues now show that such repair can occur in cells, as free tubulin dimers can be incorporated into a damaged microtubule lattice to promote rescue events.
Using a chemical screening approach, Yang and colleagues identify PKC as a regulator of lysosome biogenesis, which controls the subcellular localization of TFEB and ZKSCAN3 through parallel signalling pathways and independently of mTORC1.
Johnson et al. report that loss of leukaemia inhibitory factor receptor (LIFR) signalling reduces the expression of genes associated with dormancy in metastatic breast cancer cells, and promotes bone marrow colonization and osteoclastogenesis.
Pan et al. find that regional glutamine deficiency in melanoma tumours induces tumour cell dedifferentiation and confers therapeutic resistance through histone methylation changes.
Guesdon et al. characterize the microtubule-end-binding region of EB1 using cryo-electron tomography, providing insights into the mechanism of this interaction and the architectural changes in the GTP-cap region during microtubule growth.
