In Cancer Cell this week, an international team of researchers says that normally incompatible gene pathways are co-expressed in the genesis of retinoblastoma. Human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, mainly amacrine or horizontal interneurons, retinal progenitor cells, and photoreceptors, the authors write. Single-cell gene expression array analysis shows that the specific developmental pathways of these multiple cell types are co-expressed in individual retinoblastoma cells, creating a hybrid progenitor cell. "Neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro," the team adds.
Also in Cancer Cell this week, a team led by researchers at the University of Michigan presents a study of the regulation of polycomb group complexes by microRNAs in cancer. Epigenetic regulation mediated by polycomb repressive complexes PRC1 and PRC2 is critical for maintaining cellular homeostasis. Members of polycomb group proteins like EZH2, which is a component of PRC2, are upregulated in various cancer types. In this study, the team found several miRNAs that are repressed by EZH2 — these miRNAs are charged with regulating the expression of PRC1 proteins. "We found that ectopic over-expression of EZH2-regulated miRNAs attenuated cancer cell growth and invasiveness, and abrogated cancer stem cell properties," the authors write. "Importantly, expression analysis revealed an inverse correlation between miRNA and PRC protein levels in cell culture and prostate cancer tissues."
And finally in Cancer Cell this week, researchers at the Massachusetts General Hospital Cancer Center and Genentech say that neuregulin-1-mediated autocrine signaling can dictate sensitivity to HER2 kinase inhibitors in some cancers. The team profiled almost 700 human cancer cell lines and identified a subset of non-HER2 amplified cancer cells with a particular sensitivity to HER2 kinase inhibition. These cells, the team found, depend on an NRG1-mediate autocrine loop which drives HER3 activation, and which can be disrupted by HER2 kinase inhibitors like lapatinib. "Elevated NRG1 expression and activated HER3 are strongly associated with lapatinib sensitivity in vitro, and these biomarkers were enriched in a subset of primary head and neck cancer samples," the authors write. "The findings suggest that patients with NRG1-driven tumors lacking HER2 amplification may derive significant clinical benefit from HER2:HER3-directed therapies."