title: LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6.
abstract: Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.
authors.affiliation: 1] Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany [2] Universität Freiburg, Fakultät für Biologie, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ketscher
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
authors.forename: C A
authors.initials: CA
authors.lastname: Jilg
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Willmann
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hummel
authors.affiliation: Adolf-Butenandt Institut und Munich Center of Integrated Protein Science (CIPS), Ludwig-Maximilians-Universität München, München, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Imhof
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Rüsseler
authors.affiliation: 1] Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany [2] Universität Freiburg, Fakultät für Biologie, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hölz
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Metzger
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Müller
authors.affiliation: 1] Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany [2] BIOSS Centre of Biological Signaling Studies, Albert-Ludwigs-University, Freiburg, Germany [3] Deutsches Konsortium für Translationale Krebsforschung (DKTK), Standort, Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schüle