Mael is essential for cancer cell survival and tumorigenesis through protection of genetic integrity
Metrics: PDF 973 views | HTML 1175 views | ?
Su-Hyeon Kim1, Eun-Ran Park1, Eugene Cho1, Won-Hee Jung1, Ju-Yeon Jeon1, Hyun-Yoo Joo1, Kee-Ho Lee1, Hyun-Jin Shin1
1Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea
Kee-Ho Lee, email: firstname.lastname@example.org
Hyun-Jin Shin, email: email@example.com
Keywords: Mael, oncogenic transformation, genetic integrity, oncogene, ATM
Received: May 02, 2016 Accepted: November 21, 2016 Published: December 01, 2016
Germ line-specific genes are activated in somatic cells during tumorigenesis, and are accordingly referred to as cancer germline genes. Such genes that act on piRNA (Piwi-interacting RNA) processing play an important role in the progression of cancer cells. Here, we show that the spermatogenic transposon silencer maelstrom (Mael), a piRNA-processing factor, is required for malignant transformation and survival of cancer cells. A specific Mael isoform was distinctively overexpressed in diverse human cancer cell lines and its depletion resulted in cancer-specific cell death, characterized by apoptosis and senescence, accompanied by an increase in reactive oxygen-species and DNA damage. These biochemical changes and death phenotypes induced by Mael depletion were dependent on ATM. Interestingly Mael was essential for Myc/Ras-induced transformation, and its overexpression inhibited Ras-induced senescence. In addition, Mael repressed retrotransposon activity in cancer cells. These results suggest that Mael depletion induces ATM-dependent DNA damage, consequently leading to cell death specifically in cancer cells. Moreover, Mael possesses oncogenic potential that can protect against genetic instability.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.