Microrna

p53-mediated activation of miRNA34 candidate tumour-suppressor genes Bommer, G. T. et al. Curr. Biol. 17, 1298–1307 (2007)

Bommer et al. found that p53 can directly regulate transcription of the miR-34 family of microRNAs (miRNAs) in cell lines and mice. Transcriptional arrays on colon cancer cell lines showed that these miRNAs primarily downregulate cell-cycle-associated genes. Although miR-34s induced cell-cycle arrest, they also decreased the levels of the anti-apoptotic protein BCL2, and therefore seem to mediate two key p53 functions. The expression of two miR-34s was significantly reduced in 6 of 14 non-small-cell lung cancer (NSCLC) samples, and ectopic expression of miR-34 in NSCLC cell lines inhibited their growth.

Prostate cancer

A secreted isoform of ERBB3 promotes osteonectin expression in bone and enhances the invasiveness of prostate cancer cells Chen, N. et al. Cancer Res. 67, 6544–6548 (2007)

Prostate cancer preferentially metastasizes to bone. Previously, a secreted isoform of ERBB3 (p45-sERBB3) was detected in metastatic prostate cancer cells isolated from patients and was shown to interact with osteoblasts. Chen et al. now show that p45-sERBB3 stimulates mouse bone to secrete factors including osteonectin, which increases the invasiveness of prostate cancer cells in vitro. Invasion induced by p45-sERBB3 was also blocked by osteonectin antibodies. Thus, p45-sERBB3 and osteonectin might mediate the interactions between metastasizing prostate cancer cells and bone.

Stem cells

Tumour growth need not be driven by rare cancer stem cells Kelly, P. N. et al. Science 317, 337 (2007)

Kelly et al. challenge the hypothesis that growth of acute myeloid leukaemia is always sustained by a rare cancer stem cell. By titrating numbers of mouse pre-B/B lymphoma cells into non-irradiated histocompatible recipient mice, they showed that all mice developed disseminated lymphoma regardless of the number of cells injected. They suggest that mouse lymphomas can be maintained by a relatively large proportion of tumour cells, and that results of previous studies might reflect the need to co-transfer essential human support cells when using immunocompromised mice as a model.

Oncogenes

Wild-type NRAS and KRAS perform distinct functions during transformation Fotiadou, P. P. et al. Mol. Cell. Biol. 16 July 2007 (doi: 10.1128/MCB.00234201107)

Why do cells express two or more wild-type Ras isoforms? Fotiadou et al. used a genetically-defined system of mouse embryo fibroblasts to show that both wild-type KRAS and NRAS are essential for transformation. This is because they have distinct functions: KRAS coordinates motility by signalling through Akt and CDC42, whereas NRAS regulates adhesion by signalling through Raf and RHOA.