PMID- 35053442
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220130
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 2
DP  - 2022 Jan 7
TI  - Increased Expression and Altered Cellular Localization of Fibroblast Growth 
      Factor Receptor-Like 1 (FGFRL1) Are Associated with Prostate Cancer Progression.
LID - 10.3390/cancers14020278 [doi]
LID - 278
AB  - 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.
FAU - Yu, Lan
AU  - Yu L
AUID- ORCID: 0000-0002-7087-0883
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
FAU - Toriseva, Mervi
AU  - Toriseva M
AUID- ORCID: 0000-0003-3024-6282
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
FAU - Afshan, Syeda
AU  - Afshan S
AUID- ORCID: 0000-0002-2939-8847
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
FAU - Cangiano, Mario
AU  - Cangiano M
AD  - GenomeScan, 2333 BZ Leiden, The Netherlands.
FAU - Fey, Vidal
AU  - Fey V
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
FAU - Erickson, Andrew
AU  - Erickson A
AD  - Nuffield Department of Surgical Sciences, University of Oxford, Oxford 0X3 9DU, 
      UK.
FAU - Seikkula, Heikki
AU  - Seikkula H
AUID- ORCID: 0000-0001-9942-1582
AD  - Department of Urology, University of Turku and Turku University Hospital, 20520 
      Turku, Finland.
FAU - Alanen, Kalle
AU  - Alanen K
AD  - Department of Pathology, Turku University Hospital, 20520 Turku, Finland.
FAU - Taimen, Pekka
AU  - Taimen P
AUID- ORCID: 0000-0001-8849-4604
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
AD  - Department of Pathology, Turku University Hospital, 20520 Turku, Finland.
FAU - Ettala, Otto
AU  - Ettala O
AD  - Department of Urology, University of Turku and Turku University Hospital, 20520 
      Turku, Finland.
FAU - Nurmi, Martti
AU  - Nurmi M
AD  - Department of Urology, University of Turku and Turku University Hospital, 20520 
      Turku, Finland.
FAU - Bostrom, Peter J
AU  - Bostrom PJ
AD  - Department of Urology, University of Turku and Turku University Hospital, 20520 
      Turku, Finland.
FAU - Kallajoki, Markku
AU  - Kallajoki M
AD  - Department of Pathology, Turku University Hospital, 20520 Turku, Finland.
FAU - Tuomela, Johanna
AU  - Tuomela J
AUID- ORCID: 0000-0003-4390-4563
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
FAU - Mirtti, Tuomas
AU  - Mirtti T
AUID- ORCID: 0000-0003-0455-9891
AD  - HUS Diagnostic Center and Research Program in Systems Oncology (ONCOSYS), 
      Helsinki University Hospital and University of Helsinki, 00014 Helsinki, Finland.
FAU - Beumer, Ines J
AU  - Beumer IJ
AUID- ORCID: 0000-0002-6304-1841
AD  - GenomeScan, 2333 BZ Leiden, The Netherlands.
FAU - Nees, Matthias
AU  - Nees M
AUID- ORCID: 0000-0002-9034-301X
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
AD  - Department of Biochemistry and Molecular Biology, Medical University in Lublin, 
      20-093 Lublin, Poland.
FAU - Harkonen, Pirkko
AU  - Harkonen P
AD  - Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and 
      Turku University Hospital, 20520 Turku, Finland.
LA  - eng
GR  - 721746/The European Commission -funded Transpot H2020-MSCA-ITN program/
GR  - 267326/Academy of Finland/
GR  - 2011616008/China Scholarship Council/
PT  - Journal Article
DEP - 20220107
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8796033
OTO - NOTNLM
OT  - FGFR signaling
OT  - FGFRL1 (FGFR5)
OT  - biochemical recurrence
OT  - prostate cancer
OT  - prostate cancer progression
OT  - tumor-stromal interactions
COIS- The authors declare no potential conflict of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2022/01/07
CRDT- 2022/01/21 01:05
PHST- 2021/11/25 00:00 [received]
PHST- 2021/12/28 00:00 [revised]
PHST- 2021/12/29 00:00 [accepted]
PHST- 2022/01/21 01:05 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2022/01/07 00:00 [pmc-release]
AID - cancers14020278 [pii]
AID - cancers-14-00278 [pii]
AID - 10.3390/cancers14020278 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Jan 7;14(2):278. doi: 10.3390/cancers14020278.