Research Highlights

Short, accessible synopses of recent important articles concerning signalling pathways.

February 2009

• Inflammation: Orchestrating metastasis

  

  It is becoming increasingly clear that cancer cells play an active part in stimulating bone-marrow-derived cells (BMDCs) to create a microenvironment that is favourable for metastasis (the metastatic niche). However, the mechanisms controlling this process are not well understood. Michael Karin and colleagues have uncovered a new pathway between cancer cells and BMDCs that leads to increased metastasis.

  Original research paper Nature Reviews Cancer 9 76 doi:10.1038/nrc2598

• Cell migration: Calcium flickers at the front

  

  Calcium has a major role in directional sensing, cytoskeleton remodelling, force generation and focal adhesion relocation. Migrating cells display a rear-to-front calcium gradient with the lowest concentration at the front. However, this is controversial, as numerous effector proteins that require high calcium levels for activation reside at the cell front. In Nature, Heping Cheng and colleagues now report that high-calcium microdomains (calcium flickers) that are required for directional movement occur at the front of migrating fibroblasts.

  Original research paper Nature Reviews Molecular Cell Biology 10 86 - 87 doi:10.1038/nrm2625

• Cancer stem cells: Can mutated stem cells produce tumours?

  

  Which cells need to be mutated in order for solid tumours to fully develop? Many have postulated that mutation of a normal tissue stem cell might be required for both tumour initiation and progression, whereas others have argued that mutations in progenitor cells can induce stem cell-like qualities, giving rise to long-lived and clinically manifest disease. Two papers recently published in Nature add thought-provoking data to this debate.

  Original research paper Nature Reviews Cancer 9 74 doi:10.1038/nrc2593

• Technology: Indirect activation

  

  Tyrosine kinase activation is an important oncogenic mechanism; however, it can be difficult to detect indirect mechanisms of tyrosine kinase activation that are not caused by sequence changes in the kinases themselves. A recent study describes a new high-throughput, cost-effective approach that can systematically identify activated tyrosine kinases in cancer cells irrespectively of the mechanism of kinase activation.

  Original research paper Nature Reviews Cancer 9 75 doi:10.1038/nrc2592

• Neurodegenerative disease: Joining the dots

  

  There are signs that postmitotic neurons initiate cell cycle re-entry in several neurodegenerative disorders; however, the mechanisms by which this occurs are unclear. Similarly, although DNA damage is thought to contribute to neuronal death in many conditions, the factors that underlie this damage are poorly understood. In their new paper, Tsai and colleagues provide a mechanistic link between cell cycle re-entry, DNA damage and neuronal cell death.

  Original research paper Nature Reviews Neuroscience 10 81 doi:10.1038/nrn2577