TGF-β regulates the release of breast cancer cell-derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression.

Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. The cytokine transforming growth factor-β (TGF-β) facilitates cancer progression via EVs secreted by cancer cells, which act on recipient cells in the tumour microenvironment. However, the mechanisms of how TGF-β affects cancer cell EV release and composition are incompletely understood.

EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion.

Epithelial-to-mesenchymal transitions (EMT) and unjamming transitions provide two distinct pathways for cancer cells to become invasive, but it is still unclear to what extent these pathways are connected. Here, we addressed this question by performing 3D spheroid invasion assays on epithelial-like (A549) and mesenchymal-like (MV3) cancer cell lines in collagen-based hydrogels, where we varied both the invasive character of the cells and matrix porosity. We found that the onset time of invasion was correlated with the matrix porosity and vimentin levels, while the spheroid expansion rate correlated with MMP1 levels.

The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding.

The immunoregulatory cytokine TGF-β is pleiotropic due to the near-ubiquitous expression of the TGF-β receptors TβRI and TβRII on diverse cell types. The helminth parasite Heligmosomoides polygyrus has convergently evolved a family of TGF-β mimics (TGMs) that bind both these receptors through domains 1-3 of a 5-domain protein. One member of this family, TGM4, differs from TGF-β in acting in a cell-specific manner, failing to stimulate fibroblasts, but activating SMAD phosphorylation in macrophages.

ECM1 attenuates hepatic fibrosis by interfering with mediators of latent TGF-β1 activation.

Objective: Extracellular matrix protein 1 (ECM1) serves as a gatekeeper of hepatic fibrosis by maintaining transforming growth factor-β1 (TGF-β1) in its latent form. ECM1 knockout (KO) causes latent (L) TGF-β1 activation, resulting in hepatic fibrosis with rapid mortality. In chronic liver disease (CLD), ECM1 decreases with increasing CLD severity.