title: Mael is essential for cancer cell survival and tumorigenesis through protection of genetic integrity.
abstract: 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.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Su-Hyeon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Eun-Ran
authors.initials: ER
authors.lastname: Park
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Cho
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Won-Hee
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Jeon
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Hyun-Yoo
authors.initials: HY
authors.lastname: Joo
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Shin
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D016922:Cellular Senescence; D004249:DNA Damage; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C552355:MAEL protein, human; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; Mael; genetic integrity; oncogene; oncogenic transformation