Germline factor DDX4 functions in blood‐derived cancer cell phenotypes. Issue 8 (11th July 2017)

• Record Type: Journal Article
• Authors: Schudrowitz, Natalie; Takagi, Satoshi; Wessel, Gary M.; Yajima, Mamiko
• Is Part Of: Cancer science. Volume 108:Issue 8(2017)
• Page Start: 1612
• Page End: 1619
• Publication Date: 2017-07-11
• Subjects: DDX4/Vasa -- germline factor -- human cancer cells -- RNA helicase -- translational regulation; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13299
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : DDX4 (the human ortholog of Drosophila Vasa) is an RNA helicase and is present in the germ lines of all metazoans tested. It was historically thought to be expressed specifically in germline, but with additional organisms studied, it is now clear that in some animals DDX4/Vasa functions outside of the germline, in a variety of somatic cells in the embryo and in the adult. In this report, we document that DDX4 is widely expressed in soma‐derived cancer cell lines, including myeloma (IM‐9) and leukemia (THP‐1) cells. In these cells, the DDX4 protein localized to the mitotic spindle, consistent with findings in other somatic cell functions, and its knockout in IM‐9 cells compromised cell proliferation and migration activities, and downregulated several cell cycle/oncogene factors such as CyclinB and the transcription factor E2F1. These results suggest that DDX4 positively regulates cell cycle progression of diverse somatic‐derived blood cancer cells, implying its broad contributions to the cancer cell phenotype and serves as a potential new target for chemotherapy. Abstract : Many genes that are normally expressed selectively in the germline are also expressed in various tumor types in humans. Reutilizing functions of a germline program in the somatic lineages thus has been hypothesized to contribute to increased cellular plasticity, including immortality, active cell proliferation and migrations that are also the hallmark of cancer cells. We demonstrate that DDX4 (Drosophila Vasa homolog), one of the most conserved germline factors, is essential for cell proliferation and protein synthesis of soma‐derived cancer cells. These results elucidate, at least in part, how a germline factor could contribute to somatic regulation and in some cases even to a cancer cell phenotype.