Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Division of Experimental Cancer Research, Department of Translational Medicine, Clinical Research Centre, Lund University, Malmö, Sweden.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Show others and affiliations
2022 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261Article in journal (Refereed) Published
Abstract [en]

Low-affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) is a cell surface protein that belongs to a family of Fc receptors that facilitate the protective function of the immune system against pathogens. However, the role of FcγRIIIa in prostate cancer (PCa) progression remained unknown. In this study, we found that FcγRIIIa expression was present in PCa cells and its level was significantly higher in metastatic lesions than in primary tumors from the PCa cohort (P = 0.006). PCa patients with an elevated level of FcγRIIIa expression had poorer biochemical recurrence (BCR)-free survival compared with those with lower FcγRIIIa expression, suggesting that FcγRIIIa is of clinical importance in PCa. We demonstrated that overexpression of FcγRIIIa increased the proliferative ability of PCa cell line C4-2 cells, which was accompanied by the upregulation of androgen receptor (AR) and phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), which are the key players in controlling PCa progression. Conversely, targeted inhibition of FcγRIIIa via siRNA-mediated knockdown or using its inhibitory antibody suppressed growth of xenograft PC-3 and PC-3M prostate tumors and reduced distant metastasis in xenograft mouse models. We further showed that elevated expression of AR enhanced FcγRIIIa expression, whereas inhibition of AR activity using enzalutamide led to a significant downregulation of FcγRIIIa protein expression. Similarly, inhibition of PIP5K1α decreased FcγRIIIa expression in PCa cells. FcγRIIIa physically interacted with PIP5K1α and AR via formation of protein-protein complexes, suggesting that FcγRIIIa is functionally associated with AR and PIP5K1α in PCa cells. Our study identified FcγRIIIa as an important factor in promoting PCa growth and invasion. Further, the elevated activation of FcγRIII and AR and PIP5K1α pathways may cooperatively promote PCa growth and invasion. Thus, FcγRIIIa may serve as a potential new target for improved treatment of metastatic and castration-resistant PCa.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022.
Keywords [en]
AR pathway and antibody-based therapy, FcγRIIIa receptor, PIP5K1α, prostate cancer metastasis, targeted therapy
National Category
Cancer and Oncology
Research subject
Medicine; molecular medicine (genetics and pathology)
Identifiers
URN: urn:nbn:se:umu:diva-192100DOI: 10.1002/1878-0261.13166ISI: 000745727600001PubMedID: 34932854Scopus ID: 2-s2.0-85123504907OAI: oai:DiVA.org:umu-192100DiVA, id: diva2:1634177
Funder
Swedish Cancer Society, 2017-381Swedish Research Council, 2019-01318The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2013-5595The Kempe FoundationsCancerforskningsfonden i NorrlandAvailable from: 2022-02-01 Created: 2022-02-01 Last updated: 2024-03-20Bibliographically approved

Open Access in DiVA

fulltext(11109 kB)156 downloads
File information
File name FULLTEXT02.pdfFile size 11109 kBChecksum SHA-512
faea448aa7f7600ed411381d2357bca44fa2e3064b0f3cd7762d6c2d54ef8e039da0aefd9e5541620264cb0220a7de0537b4783156ef25dc94b35d6edf643eab
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Flodbring Larsson, PerKarlsson, RichardSarwar, MartuzaMiftakhova, Regina R.Wang, TianyanKhaja, Azharuddin Sajid SyedSemenas, JuliusChen, SaHedblom, AndreasAmjad, AliKumar, AnjaniWai, Sun NyuntÖhlund, DanielGrundström, ThomasPersson, Jenny L.

Search in DiVA

By author/editor
Flodbring Larsson, PerKarlsson, RichardSarwar, MartuzaMiftakhova, Regina R.Wang, TianyanKhaja, Azharuddin Sajid SyedSemenas, JuliusChen, SaHedblom, AndreasAmjad, AliKumar, AnjaniWai, Sun NyuntÖhlund, DanielGrundström, ThomasPersson, Jenny L.
By organisation
Department of Molecular Biology (Faculty of Medicine)Department of Molecular Biology (Faculty of Science and Technology)Umeå Centre for Microbial Research (UCMR)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)Department of Radiation Sciences
In the same journal
Molecular Oncology
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 231 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 668 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf