An unregulated regulator: Vasa expression in the development of somatic cells and in tumorigenesis

Abstract

Summary Growing evidence in diverse organisms shows that genes originally thought to function uniquely in the germ line may also function in somatic cells, and in some cases even contribute to tumorigenesis. Here we review the somatic functions of Vasa, one of the most conserved “germ line” factors among metazoans. Vasa expression in somatic cells is tightly regulated and often transient during normal development, and appears to play essential roles in regulation of embryonic cells and regenerative tissues. Its dysregulation, however, is believed to be an important element of tumorigenic cell regulation. In this perspectives paper, we propose how some conserved functions of Vasa may be selected for somatic cell regulation, including its potential impact on efficient and localized translational activities and in some cases on cellular malfunctioning and tumorigenesis.

Germline factor DDX4 functions in blood‐derived cancer cell phenotypes

“…On observation of the cells, we found that the DDX4 knockout cells typically formed incomplete spindles (Fig. e) and no longer proliferated significantly, which is also a consistent phenotype reported in germline stem cells and in some embryonic cells . In this study, however, we emphasize a population‐based study.…”

“…Furthermore, as DDX4 is generally not expressed in benign adult somatic cells, it could serve as a potential target to detect early steps of malignancy among heterogeneous tumors and/or for a cancer therapy in the future. Our results suggest that another germline factor, PIWI, also appears to be expressed with DDX4 in these same cancer cells, and thus may serve as important co‐target for cancer therapy.…”

“…In mammals, DDX4 is expressed in germ cells of both sexes and functions in germline formation and maintenance. Recent reports in several organisms, however, suggest that Vasa also functions in embryonic and adult somatic cells, in regenerative tissues, and, in some cases, in tumorigenic cells . Particularly, the finding of broad germline factor expression in a malignant brain tumor in the fly Drosophila melanogaster strongly supported the contention of not just germline factor presence, but of germline factor function in tumorigenic cells .…”

Amphioxus regeneration: evolutionary and biomedical implications

“…Both transcripts and protein of one of the key germline determinants in the PGCs, vasa, localise to this domain, as do nanos and piwil1 and piwil2 (Wu et al, 2011;Zhang et al, 2013;Dailey et al, 2016). Vasa plays a general role in regulating translation in the soma (Poon et al, 2016) and nanos2 has recently been shown to transiently repress translation in PGCs via inhibition of eIF1a in sea urchins (Ouhlen et al, 2017). Thus, we might expect expression of such genes in the adult regenerating tail.…”

VASA mRNA (DDX4) detection is more specific than immunohistochemistry using poly- or monoclonal antibodies for germ cells in the male urogenital tract

“…So far the mRNA VASA expression in normal somatic tissues has only been detected during embryogenesis. [ 1 ] The vas gene was originally identified in Drosophila (vasa), later in the mouse (Mouse vasa homolog, MVH) and in humans (VASA). [ 2 – 7 ] It maps on chromosome 5q and encodes a DEAD-box protein with ATP-dependent RNA-helicase activity.…”