Mael is essential for cancer cell survival and tumorigenesis through protection of genetic integrity
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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: [email protected]
Hyun-Jin Shin, email: [email protected]
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.
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