Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer
Abstract Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing...
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Nature Portfolio
2017
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oai:doaj.org-article:5300b420c15341a0b1159c45208f940e2021-12-02T12:31:47ZIdentification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer10.1038/s41598-017-05209-z2045-2322https://doaj.org/article/5300b420c15341a0b1159c45208f940e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05209-zhttps://doaj.org/toc/2045-2322Abstract Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1–16.2, containing the FBXL4 gene, which was confirmed in larger series of bone metastases by fluorescence in situ hybridisation (FISH). Loss of FBXL4 was also detected in primary tumours and it was highly associated with prognostic factors including high Gleason score, clinical stage, prostate-specific antigen (PSA) and extent of disease, as well as poor patient survival, suggesting that FBXL4 loss contributes to prostate cancer progression. We also demonstrated that FBXL4 deletion is detectable in circulating tumour cells (CTCs), making it a potential prognostic biomarker by ‘liquid biopsy’. In vitro analysis showed that FBXL4 plays a role in regulating the migration and invasion of prostate cancer cells. FBXL4 potentially controls cancer metastasis through regulation of ERLEC1 levels. Therefore, FBXL4 could be a potential novel prostate cancer suppressor gene, which may prevent cancer progression and metastasis through controlling cell invasion.Elzbieta StankiewiczXueying MaoD. Chas ManghamLei XuMarc Yeste-VelascoGabrielle FisherBernard NorthTracy ChaplinBryan YoungYuqin WangJasmin Kaur BansalSakunthala KudahettiLucy SpencerChristopher S. FosterHenrik MøllerPeter ScardinoR. Tim OliverJonathan ShamashJack CuzickColin S. CooperDaniel M. BerneyYong-Jie LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Elzbieta Stankiewicz Xueying Mao D. Chas Mangham Lei Xu Marc Yeste-Velasco Gabrielle Fisher Bernard North Tracy Chaplin Bryan Young Yuqin Wang Jasmin Kaur Bansal Sakunthala Kudahetti Lucy Spencer Christopher S. Foster Henrik Møller Peter Scardino R. Tim Oliver Jonathan Shamash Jack Cuzick Colin S. Cooper Daniel M. Berney Yong-Jie Lu Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer |
| description |
Abstract Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1–16.2, containing the FBXL4 gene, which was confirmed in larger series of bone metastases by fluorescence in situ hybridisation (FISH). Loss of FBXL4 was also detected in primary tumours and it was highly associated with prognostic factors including high Gleason score, clinical stage, prostate-specific antigen (PSA) and extent of disease, as well as poor patient survival, suggesting that FBXL4 loss contributes to prostate cancer progression. We also demonstrated that FBXL4 deletion is detectable in circulating tumour cells (CTCs), making it a potential prognostic biomarker by ‘liquid biopsy’. In vitro analysis showed that FBXL4 plays a role in regulating the migration and invasion of prostate cancer cells. FBXL4 potentially controls cancer metastasis through regulation of ERLEC1 levels. Therefore, FBXL4 could be a potential novel prostate cancer suppressor gene, which may prevent cancer progression and metastasis through controlling cell invasion. |
| format |
article |
| author |
Elzbieta Stankiewicz Xueying Mao D. Chas Mangham Lei Xu Marc Yeste-Velasco Gabrielle Fisher Bernard North Tracy Chaplin Bryan Young Yuqin Wang Jasmin Kaur Bansal Sakunthala Kudahetti Lucy Spencer Christopher S. Foster Henrik Møller Peter Scardino R. Tim Oliver Jonathan Shamash Jack Cuzick Colin S. Cooper Daniel M. Berney Yong-Jie Lu |
| author_facet |
Elzbieta Stankiewicz Xueying Mao D. Chas Mangham Lei Xu Marc Yeste-Velasco Gabrielle Fisher Bernard North Tracy Chaplin Bryan Young Yuqin Wang Jasmin Kaur Bansal Sakunthala Kudahetti Lucy Spencer Christopher S. Foster Henrik Møller Peter Scardino R. Tim Oliver Jonathan Shamash Jack Cuzick Colin S. Cooper Daniel M. Berney Yong-Jie Lu |
| author_sort |
Elzbieta Stankiewicz |
| title |
Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer |
| title_short |
Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer |
| title_full |
Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer |
| title_fullStr |
Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer |
| title_full_unstemmed |
Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer |
| title_sort |
identification of fbxl4 as a metastasis associated gene in prostate cancer |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/5300b420c15341a0b1159c45208f940e |
| work_keys_str_mv |
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