hPCL3S promotes proliferation and migration of androgen-independent prostate cancer cells
Polycomb repressive complex 2 (PRC2) allows the deposition of H3K27me3. PRC2 facultative subunits modulate its activity and recruitment such as hPCL3/PHF19, a human ortholog of Drosophila Polycomb-like protein (PCL). These proteins contain a TUDOR domain binding H3K36me3, two PHD domains and a "Winged-helix" domain involved in GC-rich DNA binding. The human PCL3 locus encodes the full-length hPCL3L protein and a shorter isoform, hPCL3S containing the TUDOR and PHD1 domains only. In this study, we demonstrated by RT-qPCR analyses of 25 prostate tumors that hPCL3S is frequently up-regulated. In addition, hPCL3S is overexpressed in the androgen-independent DU145 and PC3 cells, but not in the androgen-dependent LNCaP cells. hPCL3S knockdown decreased the proliferation and migration of DU145 and PC3 whereas its forced expression into LNCaP increased these properties. A mutant hPCL3S unable to bind H3K36me3 (TUDOR-W50A) increased proliferation and migration of LNCaP similarly to wt hPCL3S whereas inactivation of its PHD1 domain decreased proliferation. These effects partially relied on the up-regulation of genes known to be important for the proliferation and/or migration of prostate cancer cells such as S100A16, PlexinA2, and Spondin1. Collectively, our results suggest hPCL3S as a new potential therapeutic target in castration resistant prostate cancers.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Oncotarget - 11(2020), 12 vom: 24. März, Seite 1051-1074 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abdelfettah, Souhila [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 09.04.2020 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.18632/oncotarget.27511 |
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| Förderinstitution / Projekttitel: |
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NLM308422643 |
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| 520 | |a Polycomb repressive complex 2 (PRC2) allows the deposition of H3K27me3. PRC2 facultative subunits modulate its activity and recruitment such as hPCL3/PHF19, a human ortholog of Drosophila Polycomb-like protein (PCL). These proteins contain a TUDOR domain binding H3K36me3, two PHD domains and a "Winged-helix" domain involved in GC-rich DNA binding. The human PCL3 locus encodes the full-length hPCL3L protein and a shorter isoform, hPCL3S containing the TUDOR and PHD1 domains only. In this study, we demonstrated by RT-qPCR analyses of 25 prostate tumors that hPCL3S is frequently up-regulated. In addition, hPCL3S is overexpressed in the androgen-independent DU145 and PC3 cells, but not in the androgen-dependent LNCaP cells. hPCL3S knockdown decreased the proliferation and migration of DU145 and PC3 whereas its forced expression into LNCaP increased these properties. A mutant hPCL3S unable to bind H3K36me3 (TUDOR-W50A) increased proliferation and migration of LNCaP similarly to wt hPCL3S whereas inactivation of its PHD1 domain decreased proliferation. These effects partially relied on the up-regulation of genes known to be important for the proliferation and/or migration of prostate cancer cells such as S100A16, PlexinA2, and Spondin1. Collectively, our results suggest hPCL3S as a new potential therapeutic target in castration resistant prostate cancers | ||
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| 700 | 1 | |a Dubuissez, Marion |e verfasserin |4 aut | |
| 700 | 1 | |a Spruyt, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia, Sara P |e verfasserin |4 aut | |
| 700 | 1 | |a Rengarajan, Shruthi |e verfasserin |4 aut | |
| 700 | 1 | |a Loison, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Leroy, Xavier |e verfasserin |4 aut | |
| 700 | 1 | |a Rivera, Miguel N |e verfasserin |4 aut | |
| 700 | 1 | |a Leprince, Dominique |e verfasserin |4 aut | |
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