Microrna

Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer Varambally, S. et al. Science 13 Nov 2008 (doi: 10.1126/science.1165395)

The histone methyltransferase enhancer of zest homolog 2 (EZH2) is overexpressed in solid tumours, but the mechanisms by which this overexpression occurs were previously unclear. Now, a study has shown that a microRNA, miR-101, regulates EZH2 expression. miR-101 expression was inversely correlated with EZH2 expression and metastasis in prostate cancers. Somatic loss of the miR-101 genomic locus was observed in many solid prostate tumours, suggesting that reintroduction of miR-101 into tumour cells could restore the normal epigenetic programme.

Tumorigenesis

Inhibition of PAX3 by TGF-β modulates melanocyte viability Yang, G. et al. Mol. Cell 32, 554–563 (2008)

PAX3, a member of the paired-box transcription factor family, is important in melanocyte survival, proliferation and differentiation. A recent study has provided insights into PAX3 regulation by showing that transforming growth factor-β (TGFβ) suppresses PAX3 transcription. TGFβ levels in keratinocytes are reduced by ultraviolet irradiation, leading to upregulation of PAX3 in melanocytes and the production of melanin. PAX3 expression correlates with sun exposure and clinical characteristics in melanoma patients, indicating that PAX3 could be a viable therapeutic target for prevention of malignant melanoma.

Leukaemia

Eradication of acute promyelocytic leukemia-initiating cells through PML–RARA degradation Nadr, R. et al. Nature Med. 23 Nov 2008 (doi: 10.1038/nm.1891)

Differentiation arrest caused by the promyelocytic leukaemia (PML) and retinoic acid receptor-α (RARA) fusion protein in acute promyelocytic leukaemia (APL) can be targeted by retinoic acid. A new study shows that retinoic acid also leads to the growth arrest and loss of leukaemia-initiating cells (LICs) and these events are separable from retinoic acid-induced differentiation in a mouse model of APL. PML–RARA degradation and cyclic AMP signalling are necessary for retinoic acid-induced LIC clearance, so agents that activate cAMP along with retinoic acid might improve APL therapy.

Tumour suppressors

The tumor suppressor gene ARH1 regulates autophagy and tumor dormancy in human ovarian cancer cells Lu, Z. et al. J. Clin. Invest. 118, 3917–3929 (2008)

The role of autophagy in cancer is controversial, as it contributes to both cancer cell death and survival. A recent study shows that induction of the tumour suppressor aplasia Ras homolog member 1 (ARH1) leads to autophagic ovarian cancer cell death in vitro. By contrast, ARH1-induced autophagy is a mechanism of tumour survival and dormancy in a xenograft mouse model, indicating that the tumour microenvironment influences the role of autophagy in cancer.