Metastasis

Transforming growth factor-β signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Siegel P. M. et al. Proc. Natl Acad. Sci. USA 100, 8430–8435 (2003)

There is evidence that primary tumour cells can reprogramme their response to TGF-β, turning this tumour suppressor into a metastasis-inducing factor. Siegel et al. used transgenic mouse models to show that expression of the activated NEU receptor tyrosine kinase (also known as ERBB2/HER2) plus the activated type I TGF-β receptor suppressed mammary tumour growth, promoting pulmonary metastasis by specifically enhancing extravasation of cancer cells, while impairing tumour growth.

Tumorigenesis

The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Holbro, T. et al. Proc. Natl Acad. Sci. USA 100, 8933–8938 (2003)

For ERBB2 to function as a receptor tyrosine kinase, it must dimerize with another member of the ERBB family. As ERBB2-expressing tumours co-express ERBB3, Holbro et al. investigated whether ERBB3 is required for transformation. Suppressing ERBB3 expression in ERBB2-overexpressing breast cancer cells blocked proliferation, which could be restored by expression of constitutively active protein-kinase B. Targeted disruption of this heterodimer could prove useful for the treatment of breast cancer.

Tumour Suppressors

p53- and Mdm2-independent repression of NFκB transactivation by the ARF tumor suppressor. Rocha, S., Campbell, K. J. & Perkins, N. D. Mol. Cell 12, 15–25 (2003)

Activity of the NFκB family of transcription factors, particularly RELA, is associated with tumorigenesis and represses p53 function. Rocha et al. predicted that ARF might alter RELA activity to improve its function as a tumour suppressor. They showed that ARF causes RELA to associate with the histone deacetylase HDAC1, which represses transcription of RELA. More importantly, ARF represses the transcriptional activity of RELA in response to the oncogene BCR-ABL.

Metastasis

Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Michael Beil et al. Nature Cell Biol. 24 Aug 2003 (doi: 10.1038ncb1037)

Sphingosylphosphorylcholine (SPC) is a biologically active lipid that is found at increased concentrations in the blood and malignant ascites of patients with ovarian cancer. The authors show that SPC reorganizes keratin filaments, which increases the elasticity of cells and therefore aids their migration. So, SPC might facilitate migration of cells during metastasis.