Research Highlights

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

June 2009

• Genomics: A modular approach to signalling

  

  Instead of considering signalling in terms of a linear sequence, the concept of modules as units of signalling activity is a useful way to represent complex biological networks, such as those involved in cancer. A recent study describes an approach to dissect oncogenic signalling pathways into functional modules on the basis of gene expression signatures, which can then be used to analyse disease outcome and responses to therapeutics.

  Original research paper Nature Reviews Cancer 9 387 doi:10.1038/nrc2667

• Cell migration: Talin heads off

  

  Talin is essential for integrin activation and the formation of focal adhesions. In migrating cells, talin is cleaved by calpain into a rod domain and a head domain that binds β integrin tails. The head domain contains a potential phosphorylation site for CDK5 – a kinase that is known to influence cell migration. Reporting in Nature Cell Biology, Mark Ginsberg, Ken Jacobson and colleagues now show that CDK5-dependent phosphorylation of the head domain of talin regulates its ubiquitylation and degradation through the E3 ubiquitin ligase SMURF1, thus controlling adhesion turnover and migration.

  Original research paper Nature Reviews Molecular Cell Biology 10 368 - 369 doi:10.1038/nrm2702

• Metastasis: Attack of the mutant p53

  

  The molecular details of how transforming growth factor-β (TGFβ) can both inhibit tumorigenesis and promote metastasis are unclear. Stefano Piccolo and colleagues describe a new pathway that suggests opposing roles for mutant p53 and wild-type p63 in TGFβ-induced metastasis and uncover a gene signature that could be clinically useful for predicting breast cancer prognosis.

  Original research paper Nature Reviews Cancer 9 384 - 385 doi:10.1038/nrc2658

• Tumour Suppressors: Multi-tasking

  

  Retinoblastoma 1 (RB1) was the first tumour suppressor gene to be identified and is required to limit the activity of E2f transcription factors and prevent proliferation. However, the function of RB has proved to be more complex, as three recent papers have highlighted.

  Original research paper Nature Reviews Cancer 9 384 - 385 doi:10.1038/nrc2660

• Therapy: FGFR3 is key

  

  Overexpression of fibroblast growth factor receptor 3 (FGFR3) has been shown to drive oncogenesis in a subset of patients with multiple myeloma. However, epithelial cancers — such as bladder cancer — also exhibit deregulation and mutation of FGFR3, but whether this contributes to tumorigenesis in vivo has remained unclear.

  Original research paper Nature Reviews Cancer 9 386 - 387 doi:10.1038/nrc2669

• T cell differentiation: The T_H1 two step

  

  The cytokines interferon-γ (IFNγ) and interleukin-12 (IL-12) and the transcription factor T-bet are essential for T helper 1 (T_H1) cell differentiation. But how do these three factors cooperate to induce and stabilize the T_H1 cell phenotype? Now, Höfer and colleagues describe a two-step model of positive feedback regulation for T_H1 cell differentiation that is mediated first by a T cell receptor (TCR)-IFNγ-T-bet signalling loop and then by an IL-12-T-bet signalling loop.

  Original research paper Nature Reviews Immunology 9 387 doi:10.1038/nri2571