Standfirst
A new study shows that one of numerous functions of the tumour suppressor p53 might be to limit the invasive potential of cells through the regulation of the transcription factor slug.
Metastasis
The tumour suppressor p53 has many functions, and this paper indicates that it might also limit the invasive potential of cells. Wild-type p53 is involved in the regulation of the transcription factor slug, which induces epithelial to mesenchymal transition in normal and cancer cells. Wild-type p53 increases the expression of MDM2 and forms a p53–MDM2–slug complex, resulting in MDM2-mediated degradation of slug. However, in non-small-cell lung cancer cell lines mutant p53 cannot form this complex, which leads to the stabilization of slug. In addition, patients with non-small-cell lung cancer that express mutant p53 have reduced levels of MDM2, increased expression of slug and a poor prognosis.
Tumorigenesis
and colonic tumorigenesisThe contribution of peroxisome proliferator-activated receptor-
(PPAR) to colorectal cancer has been clarified by a new mouse model. Deletion of exon 4 of Ppard in epithelial cells of the colon resulted in mice that developed 98.5% fewer tumours than wild-type mice treated with the inflammatory mediator azoxymethane. Levels of vascular endothelial growth factor were also reduced compared with tumours arising in wild-type mice. Thus, PPAR seems to contribute substantially to tumorigenesis induced by azoxymethane.
Non-coding RNA
The expression of the let-7 family of microRNAs is repressed in several cancers, but how is this global repression induced? The non-coding RNAs LIN28 and LIN28B are known to prevent the processing of let-7 family members to mature microRNAs. This paper shows that LIN28 and LIN28B are overexpressed in 15% of primary human tumours and cell lines, and this correlates with decreased expression of let-7 microRNAs. LIN28 and LIN28B transform cell lines when overexpressed and are also expressed in several human tumours of a more advanced stage.
Tumour initiation
Loss of the tumour suppressor gene neurofibromatosis 1 (NF1) results in the development of neural and dermal fibromas. These authors show that Nf1-deficient skin neural precursor cells can form plexiform and dermal neurofibromas in mice. Importantly, loss of NF1 is necessary, but not sufficient, for Nf1-deficient skin neural precursor cells to form dermal neurofibromas in mouse models, indicating that the microenvironment, including neurons and hormones, makes a substantial contribution to tumour formation.
