Research Papers:

hPCL3S promotes proliferation and migration of androgen-independent prostate cancer cells

Souhila Abdelfettah, Gaylor Boulay, Marion Dubuissez, Nathalie Spruyt, Sara P. Garcia, Shruthi Rengarajan, Ingrid Loison, Xavier Leroy, Miguel N. Rivera and Dominique Leprince _

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Oncotarget. 2020; 11:1051-1074. https://doi.org/10.18632/oncotarget.27511

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Souhila Abdelfettah4, Gaylor Boulay1, Marion Dubuissez3, Nathalie Spruyt4, Sara P. Garcia1, Shruthi Rengarajan1, Ingrid Loison4, Xavier Leroy2, Miguel N. Rivera1 and Dominique Leprince4

1 Department of Pathology, Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA

2 Department of Pathology, University de Lille, CHU de Lille, F-59000 Lille, France

3 Present Address: Maisonneuve-Rosemont Hospital Research Center, Maisonneuve-Rosemont Hospital, Montreal, QC H1T 3W5, Canada

4 University de Lille, CNRS, Institut Pasteur de Lille, UMR 8161m M3T, Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France

Correspondence to:

Dominique Leprince,email: [email protected]

Keywords: hPCL3S; PHF19; PRC2; β-catenin; prostate cancer

Received: September 19, 2019     Accepted: February 17, 2020     Published: March 24, 2020


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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