Research Highlights

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

January 2009

• Signalling: ERBB2 hangs in the balance

  

  The resistance of oestrogen receptor (ER)-positive breast cancers to tamoxifen is associated with increased expression levels of the oncogene ERBB2. The molecular mechanism that links ER signalling, ERBB2 expression and tamoxifen resistance has remained elusive. However, Jason Carroll and colleagues report in Nature that ERBB2 expression can be controlled by the ER co-activator AIB1 (amplified in breast cancer 1) and the transcription factor PAX2 (paired box 2 protein), and the differential expression of these two proteins determines the response to tamoxifen.

  Original research paper Nature Reviews Cancer 9 12 - 13 doi:10.1038/nrc2570

• Metastasis: Moved to act

  

  The Rho family of small GTPases is known to be important for the regulation of cell motility. A recent paper by Chris Marshall and colleagues published in Cell has shown that differential activation of Rac and Rho determines the type of movement that a cell uses.

  Original research paper Nature Reviews Cancer 9 3 doi:10.1038/nrc2564

• Cell polarity: Morphogenesis is the key

  

  Polarization of luminal mammary epithelial cells is crucial for normal function and there is accumulating evidence that regulators of polarity, such as scribble (SCRIB), are lost or deregulated in the early stages of carcinoma development. Senthil Muthuswamy and colleagues have now elucidated a mechanism for the transforming effect of SCRIB loss that may be applicable to the loss of other polarity regulators.

  Original research paper Nature Reviews Cancer 9 10 - 11 doi:10.1038/nrc2576

• Angiogenesis: Renaissance molecule

  

  Vascular endothelial growth factor A (VEGFA) has an important role in angiogenesis. However, exactly how VEGFA affects the various cell types that are involved in the formation of blood vessels is not clear. Two papers published in Nature have shed more light on the functions of this versatile molecule and its role in tumorigenesis.

  Original research paper Nature Reviews Cancer 9 10 - 11 doi:10.1038/nrc2568

• Tumorigenesis: Can you have too much MYC?

  

  The proto-oncogene MYC can activate tumour suppressor responses (ARF–p53, apoptosis or senescence) or proliferation, but what discriminates between these opposing biological outputs? Gerard Evan and colleagues now show that thresholds exist for the activation of each response, which has implications for the selective pressure that determines tumour progression.

  Original research paper Nature Reviews Cancer 9 4 - 5 doi:10.1038/nrc2578