F-box protein interactions with the hallmark pathways in cancer

Randle, Suzanne J.; Laman, Heike

doi:10.1016/j.semcancer.2015.09.013

Cited by 73 publications

(46 citation statements)

References 247 publications

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“…Increase of ROC-1 expression from early to advanced BC, supports its poor prognostic impact and implies a potential role in BC progression. ROC-1 overexpression significant association with desmoplastic stroma was consistent with others supporting the role of ROC-1 as an EMT [17][18][19]. Knockdown of ROC-1 transactivates the RhoA and Rac1 signaling pathways and inhibits mTOR activity, which has a pivotal role in regulation of various cellular processes including EMT, thus causing suppression of EMT in MIBC [20][21][22][23][24].…”

Section: Discussionsupporting

confidence: 88%

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients

et al. 2020

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Background: Bladder cancer (BC) is one of the most common malignancies in Egypt, representing about 8.7% of cancers in both sexes with more predominance in males, making identification of valuable predictive and prognostic markers, mandatory. Cullin-RING ligases (CRL) play an important role in the ubiquitination of cell cycle-related proteins or other proteins (e.g., DNA replication protein, signal transduction protein). Regulator of Cullins-1 (ROC-1) is a key subunit of CRL. P21 belongs to the family of cyclin dependent kinase inhibitors (CKIs) which regulates cell cycle by inactivating Cyclin-Dependent Kinases key regulators of the cell cycle. CAIX a highly active member of the family of carbonic anhydrases has gained much interest as a hypoxic marker. Hypoxia is a consequence of the rapid growth of many tumors, including bladder cancer, and is an important regulator of gene expression and resistance to chemotherapy and radiotherapy. Therefore the purpose of this study is to evaluate the role of ROC-1, CAIX and P21 and its relationship with the clinico-pathological features of bladder cancer in Egyptian patients. Methods: Using the standard immunohistochemical technique, ROC-1, CAIX and P21 expression in 80 primary bladder carcinomas and 15 normal bladder specimens as control group were assessed. The bladder carcinoma cases included 50 cases with muscle invasive bladder cancer and 30 cases with non-muscle invasive bladder cancer. Results: Over expression of ROC-1, CAIX and P21 in BC were significantly associated with muscularis propria invasion and high grade BC. ROC-1, CAIX and P21, showed significant inverse relationship in primary BC cases. CAIX expression was significantly higher in BC compared with controls. Regarding the survival analysis, expression of ROC-1, CAIX and P21 didn't affect the survival of BC patients. Conclusions: High expression of ROC-1, CAIX and P21 could be promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy.

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Section: Discussionsupporting

confidence: 88%

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients

et al. 2020

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“…That gene belongs to the same family as FBXO7, a gene mutated in complex parkinsonisms (Di Fonzo et al, 2009;Paisan-Ruiz et al, 2010;Zhao et al, 2013) that is involved in mitochondrial homeostasis and in the ubiquitin ligase complex called SCFs (SKP1-cullin-F-box). FBXO5 is also part of the SCF complex (Randle and Laman, 2016), and our MitoTracker assay showed that FBXO5 induces mitochondrial depolarization upon silencing, suggesting a role of that gene in mitochondrial homeostasis as FBXO7 (Burchell et al, 2013).…”

Section: Discussionmentioning

confidence: 72%

An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein

Kara

Crimi

Wiedmer

et al. 2019

Preprint

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Neuropathological and experimental evidence suggests that the cell-to-cell transfer of a-synuclein has an important role in the pathogenesis of Parkinson's disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook an siRNA, genome-wide high throughput screen to identify genes regulating the cell-to-cell transfer of a-synuclein. We transiently transfected HEK cells stably overexpressing a-synuclein with a construct encoding GFP-2a-aSynuclein-RFP. The cells expressing a-synuclein-RFP through transfection were double positive for GFP and RFP fluorescence, whereas the cells receiving it through transfer were positive only for RFP fluorescence. The amount of asynuclein transfer was quantified by high content microscopy. A series of unbiased screens confirmed the involvement of 38 genes in the regulation of a-synuclein-RFP transfer. One of those hits was ITGA8, a candidate gene recently identified through a large PD genome wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) showed that the hits clustered in networks that included known PD Mendelian and GWAS risk genes more frequently than expected than random chance. Given the genetic overlap between a-synuclein transfer and PD, those findings provide supporting evidence for the importance of the cell-to-cell transfer of a-synuclein in the pathogenesis of PD, and expand our understanding of the mechanism of a-synuclein spread.

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“…Functional FBXO28 activity has also been shown to be associated with adverse breast cancer prognosis, and correlates with TP53 mutation status specifically in ER-positive breast tumors [19, 20]. FBXO28 belongs to the F-box family of proteins that determine the substrate specificity of the SCF ubiquitin ligase complex, a regulatory system that plays a critical role in tumorigenesis [21, 22]. SCF-FBXO28 specifically ubiquitylates Myc, promoting Myc-p300 transcriptional activity and subsequent oncogenic signaling [19].…”

Section: Discussionmentioning

confidence: 99%

TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer

Fagerholm¹,

Khan²,

Schmidt³

et al. 2017

Oncotarget

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TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828). For SNPs interacting with anthracycline treatment, siRNA knockdown experiments were carried out to validate candidate genes.In the test for interaction between SNP genotype and TP53 status, we identified one locus, represented by rs10916264 (p(interaction) = 3.44 05E010-5; FDR-adjusted p = 0.0011) in estrogen receptor (ER) positive cases. The rs10916264 AA genotype associated with worse survival among cases with ER-positive, TP53-positive tumors (hazard ratio [HR] 2.36, 95% confidence interval [C.I] 1.45 - 3.82). This is a cis-eQTL locus for FBXO28 and TP53BP2; expression levels of these genes were associated with patient survival specifically in ER-positive, TP53-mutated tumors. Additionally, the SNP rs798755 was associated with survival in interaction with anthracycline treatment (p(interaction) = 9.57 05E010-5, FDR-adjusted p = 0.0130). RNAi-based depletion of a predicted regulatory target gene, FAM53A, indicated that this gene can modulate doxorubicin sensitivity in breast cancer cell lines.If confirmed in independent data sets, these results may be of clinical relevance in the development of prognostic and predictive marker panels for breast cancer.

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F-box protein interactions with the hallmark pathways in cancer

Cited by 73 publications

References 247 publications

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients

An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein

TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer

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