Refereed journal article or data article (A1)

Increased Expression and Altered Cellular Localization of Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) Are Associated with Prostate Cancer Progression




List of Authors: Yu Lan, Toriseva Mervi, Afshan Syeda, Cangiano Mario, Fey Vidal, Erickson Andrew, Seikkula Heikki, Alanen Kalle, Taimen Pekka, Ettala Otto, Nurmi Martti, Boström Peter J, Kallajoki Markku, Tuomela Johanna, Mirtti Tuomas, Beumer Inès J, Nees Matthias, Härkönen Pirkko

Publisher: MDPI

Publication year: 2022

Journal: Cancers

Journal name in source: CANCERS

Journal acronym: CANCERS

Volume number: 14

Number of pages: 22

eISSN: 2072-6694

DOI: http://dx.doi.org/10.3390/cancers14020278

URL: https://www.mdpi.com/2072-6694/14/2/278

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/174866513


Abstract
Fibroblast growth factor receptors (FGFRs) 1-4 are involved in prostate cancer (PCa) regulation, but the role of FGFR-like 1 (FGFRL1) in PCa is unclear. FGFRL1 expression was studied by qRT-PCR and immunohistochemistry of patient tissue microarrays (TMAs) and correlated with clinical patient data. The effects of FGFRL1 knockdown (KD) in PC3M were studied in in vitro culture models and in mouse xenograft tumors. Our results showed that FGFRL1 was significantly upregulated in PCa. The level of membranous FGFRL1 was negatively associated with high Gleason scores (GSs) and Ki67, while increased cytoplasmic and nuclear FGFRL1 showed a positive correlation. Cox regression analysis indicated that nuclear FGFRL1 was an independent prognostic marker for biochemical recurrence after radical prostatectomy. Functional studies indicated that FGFRL1-KD in PC3M cells increases FGFR signaling, whereas FGFRL1 overexpression attenuates it, supporting decoy receptor actions of membrane-localized FGFRL1. In accordance with clinical data, FGFRL1-KD markedly suppressed PC3M xenograft growth. Transcriptomics of FGFRL1-KD cells and xenografts revealed major changes in genes regulating differentiation, ECM turnover, and tumor-stromal interactions associated with decreased growth in FGFRL1-KD xenografts. Our results suggest that FGFRL1 upregulation and altered cellular compartmentalization contribute to PCa progression. The nuclear FGFRL1 could serve as a prognostic marker for PCa patients.

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Last updated on 2022-06-07 at 15:17