Highlights of This Issue

Abstract

The apparent parallels between embryonic stem cell (ESC) self-renewal and cancer cell proliferation have raised speculation that a common network of genes may regulate these traits. Jung and colleagues identified a set of microRNAs as promoters of ESC self-renewal and liver cancer cell proliferation. These microRNAs are frequently upregulated in solid liver tumor tissues, and their overexpression in quiescent human primary hepatocytes induces EMT and activates multiple cancer-associated signaling pathways. These findings suggest that microRNAs that are essential in normal development as promoters of ESC self-renewal may harbor neoplastic transformation when they escape silencing in quiescent cellular lineages.Mast cells are recruited to many solid tumors via the stem cell factor/KIT receptor signaling axis. Within tumors, mast cell–derived mediators enhance growth of tumor vasculature and metastasis. Kwok and colleagues used a combination of in vitro and in vivo assays to show that FES kinase signaling in mast cells is required for migration toward mammary tumors and promotes tumor progression in mice. These results identify FES as a potential therapeutic target in cancers with stromal mast cell involvement.The Hippo pathway has emerged as an important component of the intricate cellular signaling network regulating cell proliferation and apoptosis. Despite the distinct evidence of loss of the NF2 gene in the majority of sporadic meningiomas, little is known about the contribution of the Hippo pathway to the development of meningeal neoplasia. Baia and colleagues examined 70 primary tumors by immunohistochemistry and found that YAP1 was highly expressed and localized to the nucleus, highlighting its activation in meningiomas. Using human cells lines and an in vivo mouse model, they investigated the role of YAP1 in meningiomas and its effects on cell proliferation, migration, apoptosis, and tumorigenesis. These findings strongly suggest that deregulation of the Hippo pathway is largely observed and that YAP1 functions as an oncogene in these tumors.Radioresistance is a major feature of erbB-overexpressing tumors with activated phosphoinositide 3-kinase/Akt signaling, stimulating DNA double-strand break repair. Toulany and colleagues describe the specific steps of how Akt interacts with DNA–protein kinase complex (DNA-PKcs), the major enzyme of the nonhomologous end-joining repair. Radiation-induced Akt activates DNA-PKcs through direct protein–protein interaction and promotes its accumulation at the DNA damage site. Subsequently, the Akt-dependent release of DNA-PKcs facilitates effective repair of radiation-induced DNA double-strand breaks and thus stimulates tumor cell survival. This mechanistic study provides the rationale to target Akt in combination with radiotherapy for resistant tumors.