Research Highlights

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

February 2008

• Signalling: The GEP100 pathway to invasion

  

  Activation of the epidermal growth factor receptor (EGFR) can lead to tumour metastasis, but it is still not clear which signalling pathways downstream of EGFR mediate invasion. In Nature Cell Biology, Hisataka Sabe and colleagues now report that the ADP-ribosylation factor (ARF) guanine nucleotide-exchange factor (GEF) ARFGEP100 induces breast cancer invasion by specifically activating the GTPase ARF6 in response to EGF.

  Original research paper Nature Reviews Cancer 8 80 - 81 doi:10.1038/nrc2319

• Cell signalling: Balancing act

  

  The disruption of key regulators that orchestrate the commitment of cells to enter the G1 phase of the cell cycle, such as retinoblastoma (RB) and members of the E2F family of transcription factors, is commonly associated with tumorigenesis. E2F transcription factors can activate genes that promote proliferation and, paradoxically, genes that induce apoptosis. Joseph Nevins and colleagues have clarified the importance of the balance between E2F1-dependent proliferation and apoptosis in cancer.

  Original research paper Nature Reviews Cancer 8 75 doi:10.1038/nrc2320

• Lipids: Orientating with PtdIns(3,4,5)P₃

  

  Just as mountaineers must orientate themselves before starting an ascent, so must cells orientate their spindles before division. But whereas mountaineers have compasses, it is not clear how cells orientate themselves. For instance, cell–cell contacts, cell-polarity cues and integrin signalling can all come into play. Now, Toyoshima et al. show that phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P₃) can act as a compass needle to orientate the spindle by coordinating dynein–dynactin motor complexes.

  Original research paper Nature Reviews Molecular Cell Biology 9 94 - 95 doi:10.1038/nrm2341

• Phagocytosis: Autophagy lends a hand

  

  A new study in Nature shows that Toll-like receptor (TLR) signalling usurps components that are traditionally associated with autophagy to increase the efficiency of phagocytosis, thereby providing a previously unappreciated link between these two ancient microbial defence mechanisms.

  Original research paper Nature Reviews Immunology 8 92 - 93 doi:10.1038/nri2258

• Innate immunity: NF-κB is not alone

  

  A new nuclear factor has been discovered that is required for innate immune responses and is highly conserved in mice and flies. The new molecule, Akirin, functions in parallel with the transcription factor NF-B (nuclear factor-B) downstream of the immune deficiency (IMD) pathway in Drosophila melanogaster, and has an essential role downstream of the Toll-like receptor (TLR), tumour-necrosis factor (TNF) and interleukin-1 (IL-1) signalling pathways that lead to the production of IL-6 in mice.

  Original research paper Nature Reviews Immunology 8 90 - 91 doi:10.1038/nri2259