Metastasis 'systems' biology: how are macro-environmental signals transmitted into microenvironmental cues for disseminated tumor cells?

Disseminated breast tumor cells reside on or near stable microvascular endothelium. Currently, the cues that disrupt DTC dormancy and facilitate outgrowth are largely unknown. This article explores the hypothesis that specific patient lifestyle exposures (e.

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease.

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations.

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury.

Background & Aims: In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration, however, the mechanism of activation in chronic liver injury is poorly understood.