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أعرض في EDS

FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer

التفاصيل البيبلوغرافية
العنوان: FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer
المؤلفون: Per Flodbring Larsson, Richard Karlsson, Martuza Sarwar, Regina Miftakhova, Tianyan Wang, Azharuddin Sajid Syed Khaja, Julius Semenas, Sa Chen, Andreas Hedblom, Amjad Ali, Kristina Ekström‐Holka, Athanasios Simoulis, Anjani Kumar, Anette Gjörloff Wingren, Brian Robinson, Sun Nyunt Wai, Nigel P. Mongan, David M. Heery, Daniel Öhlund, Thomas Grundström, Niels Ødum, Jenny L. Persson
المصدر: Molecular Oncology, Vol 16, Iss 13, Pp 2496-2517 (2022)
بيانات النشر: Wiley, 2022.
سنة النشر: 2022
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: AR pathway and antibody‐based therapy, FcγRIIIa receptor, PIP5K1α, prostate cancer metastasis, targeted therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1878-0261
1574-7891
66238242
Relation: https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261
DOI: 10.1002/1878-0261.13166
URL الوصول: https://doaj.org/article/b9424d66238242208aa13b376f19daab
رقم الأكسشن: edsdoj.b9424d66238242208aa13b376f19daab
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:18780261
15747891
66238242
DOI:10.1002/1878-0261.13166