Optical tools to study the subcellular organization of GPCR neuromodulation.

Modulation of neuronal circuit activity is key to information processing in the brain. G protein-coupled receptors (GPCRs), the targets of most neuromodulatory ligands, show extremely diverse expression patterns in neurons and receptors can be localized in various sub-neuronal membrane compartments. Upon activation, GPCRs promote signaling cascades that alter the level of second messengers, drive phosphorylation changes, modulate ion channel function, and influence gene expression, all of which critically impact neuron physiology.

Notch2 pathway mediates breast cancer cellular dormancy and mobilisation in bone and contributes to haematopoietic stem cell mimicry.

Background: Recurrence after >5-year disease-free survival affects one-fifth of breast cancer patients and is the clinical manifestation of cancer cell reactivation after persistent dormancy.

Methods: We investigated cellular dormancy in vitro and in vivo using breast cancer cell lines and cell and molecular biology techniques.

Results: We demonstrated cellular dormancy in breast cancer bone metastasis, associated with haematopoietic stem cell (HSC) mimicry, in vivo competition for HSC engraftment and non-random distribution of dormant cells at the endosteal niche.