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PiRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

ABSTRACT: Piwi proteins are normally restricted in germ cells to suppress transposons through association with piRNAs, but are also frequently activated in many types of human cancers. Of great puzzle is the lack of induction of corresponding piRNAs in cancer cells, as we document here in human pancreatic ductal adenocarcinomas (PDAC), implying that such germline-specific proteins are somehow hijacked to promote tumorigenesis through different mode of action. To pursue the underlying mechanism, we now demonstrate that in the absence of piRNAs, the aberrantly induced human PIWIL1 in PDAC functions as an oncoprotein by activating the Anaphase Promoting Complex/Cyclosome (APC/C), which then targets a critical cell adhesion-related protein Pinin to enhance PDAC metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis. These findings thus unveil an piRNA-dependent mechanism to switch PIWIL1 from a substrate in spermatids to a co-activator of APC/C in human cancer cells.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE141340 | GEO | 2020/02/01

REPOSITORIES: GEO

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Piwi proteins and piRNAs in mammalian oocytes and early embryos

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2015-03-27 | E-GEOD-64942 | biostudies-arrayexpress

Piwi proteins and piRNAs in mammalian oocytes and early embryos

2015-03-27 | GSE64942 | GEO

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piRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

Project description:piRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

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The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters

Project description:The piRNA pathway is essential for female fertility in golden hamsters and likely humans, but not in mice. However, the role of individual PIWIs in reproduction remains poorly understood outside of mice. Here, using golden hamsters, we establish dynamic expression profiles and subcellular localization for all four PIWIs and characterize their associated reproductive defects in knockout mutants. In female golden hamsters, PIWIL1 and PIWIL3 are highly expressed throughout oogenesis and early embryogenesis, while PIWIL1 knockout leads to sterility, and PIWIL3 deficiency results in subfertility with lagging zygotic development. PIWIL1 can partially compensate for TE silencing and transcriptional regulation in PIWIL3 knockout females, but not vice versa. PIWIL1 and PIWIL4 are the predominant PIWIs expressed in adult or postnatal testes, respectively, while PIWIL2 is present in both stages. Notably, in golden hamsters, none of the differences were found between pre-pachytene and pachytene piRNAs characteristic of mice. Loss of any PIWI expressed in testes leads to sterility and severe but distinct spermatogenesis disorders, which are markedly less severe in mice. These findings expand our understanding of the non-redundant PIWI-piRNA regulatory functions in gametogenesis and early embryogenesis in golden hamster, increasing the value of this model for studying human fertility.

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piRNA pathway is essential for generating functional oocytes in golden hamster

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2019-01-31 | GSE106970 | GEO

The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [small RNA-seq]

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2015-09-03 | PXD002076 | Pride

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2019-12-11 | PXD012557 | Pride

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