Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer

Zhuo, Yangjia; Xi, Mian; Wan, Yuqing; Hua, Wei; Liu, Yuanling; Song, Wan; Zhou, Yanmin; Luo, Hongwei; Wu, Shulin; Zhong, Weide; Wu, Chin‐Lee

doi:10.3892/ijmm.2015.2086

Cited by 38 publications

(29 citation statements)

References 31 publications

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“… 10 Zhuo et al described higher CENPF expression in 99 cancer samples compared with normal tissue and suggested an association with unfavorable tumor phenotype and poor prognosis. 17 Similar results were mentioned for the outcome of 821 patients with prostate cancers. 10 These promising data encouraged us to interrogate the prognostic impact of CENPF protein expression in a large set of prostate cancers.…”

Section: Introductionsupporting

confidence: 71%

Upregulation of centromere protein F is linked to aggressive prostate cancers

Göbel

Özden

Schroeder

et al. 2018

CMAR

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BackgroundCentromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer.Materials and methodsUsing a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to study its effect on prostate-specific antigen recurrence-free survival.ResultsCENPF overexpression was found in 53% of cancers, and was linked to higher Gleason grade, advanced pathological tumor stage, accelerated cell proliferation, and lymph node metastasis (p<0.0001, each). A comparison with other key molecular features accessible through the microarray revealed strong associations between CENPF overexpression and presence of erythroblast transformation-specific (ETS)-related gene (ERG) fusion as well as phosphatase and tensin homolog deletion (p<0.0001, each). CENPF overexpression was linked to early biochemical recurrence. A subset analysis revealed that this was driven by the ERG-negative subset (p<0.0001). This was independent of established preoperative and postoperative prognostic parameters in multivariate analyses.ConclusionThe results of our study identify CENPF overexpression as an important mechanism and a potential biomarker for prostate cancer aggressiveness.

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Section: Introductionsupporting

confidence: 71%

Upregulation of centromere protein F is linked to aggressive prostate cancers

Göbel

Özden

Schroeder

et al. 2018

CMAR

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“…Previous studies have demonstrated that the upregulation of CENPF may play a role in the regulation of cell division and may be used as proliferation marker of malignant cell growth in clinical practice due its localizations in the cell cycle [35–37]. It has been reported that the overexpression of CENPF associated with poor prognosis in hepatocellular carcinoma, breast cancer, colorectal gastrointestinal stromal tumors, esophageal squamous cell carcinoma and prostate cancer [38–42]. Silencing CENPF can decrease the ability of HCC cells to proliferate, form colonies and induce tumor formation in nude mice [38].…”

Section: Discussionmentioning

confidence: 99%

HIF-1α promoted vasculogenic mimicry formation in hepatocellular carcinoma through LOXL2 up-regulation in hypoxic tumor microenvironment

Wang

Zhao

Zhu

et al. 2017

J Exp Clin Cancer Res

168

133

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BackgroundThe incidence and mortality rates of hepatocellular carcinoma (HCC) have steadily increased in recent years. A hypoxic microenvironment is one of the most important characteristics of solid tumors which has been shown to promote tumor metastasis, epithelial-mesenchymal transition and angiogenesis. Epithelial-mesenchymal transition and vasculogenic mimicry have been regarded as crucial contributing factors to cancer progression. HIF-1α functions as a master transcriptional regulator in the adaptive response to hypoxia. Lysyl oxidases like 2 (LOXL2) is a member of the lysyl oxidase family, which main function is to catalyze the covalent cross-linkages of collagen and elastin in the extracellular matrix. Recent work has demonstrated that HIF-1α promotes the expression of LOXL2, which is believed to amplify tumor aggressiveness. LOXL2 has shown to promote metastasis and is correlated with poor prognosis in hepatocellular carcinoma. The purpose of our study is to explore the role of HIF-1α in progression and metastasis of hepatocellular carcinoma by promoting the expression of LOXL2 as well as the potential regulatory mechanism.MethodsHIF-1α, LOXL2 expression and CD31/periodic acid-Schiff double staining in HCC patient samples were examined by immunohistochemical staining. shRNA plasmids against HIF-1α was used to determine whether LOXL2 been increased by HIF-1α. We monitored a series of rescue assays to demonstrate our hypothesis that LOXL2 is required and sufficient for HIF-1α induced EMT and VM formation, which mediates cellular transformation and takes effect in cellular invasion. Then we performed GeneChip® Human Transcriptome Array (HTA) 2.0 in HepG2 cells, HepG2 cells overexpressed LOXL2 and HepG2 cells treated with CoCl2.ResultsIn clinical HCC tissues, it confirmed a positive relationship between HIF-1α and LOXL2 protein. Importantly, HIF-1α and LOXL2 high expression and the presence of vasculogenic mimicry were correlated to poor prognosis. HIF-1α was found to induce EMT, HCC cell migration, invasion and VM formation by regulating LOXL2. The results of microarray assays were analyzed.ConclusionHIF-1α plays an important role in the development of HCC by promoting HCC metastasis, EMT and VM through up-regulating LOXL2. This study highlights the potential therapeutic value of targeting LOXL2 for suppression of HCC metastasis and progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0533-1) contains supplementary material, which is available to authorized users.

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“…Some of these cell lines might have adapted their kinetochores to the fast pace of their divisions, possibly by becoming heavily dependent on CENP-F. Indeed, CENP-F emerges as a marker that is overexpressed in cancers (Aytes et al, 2014;Falagan et al, 2018;O'Brien et al, 2007;Zhuo et al, 2015). Here, we find that CENP-F can be downregulated without obvious consequences on animal health.…”

Section: Discussionmentioning

confidence: 59%

Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminal domain are dispensable for normal development in mice

Peterka

Kornmann

2018

Preprint

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CENP-F is a large, microtubule-binding protein that regulates multiple cellular processes including chromosome segregation and mitochondrial trafficking at cytokinesis. This multiplicity of function is mediated through the binding of various partners, like Bub1 at the kinetochore and Miro at mito-chondria. Due to the multifunctionality of CENP-F, the cellular phenotypes observed upon its depletion are difficult to interpret and there is a need to genetically separate its different functions by preventing binding to selected partners. Here we engineer a CENP-F point-mutant that is deficient in Miro binding and thus is unable to localize to mitochondria, but retains other localizations. We introduced this mutation in cultured human cells using CRISPR/Cas9 and show it causes a defect in mitochondrial spreading similar to that observed upon Miro depletion. We further create a mouse model carrying this CENP-F variant, as well as truncated CENP-F mutants lacking the farnesylated C-terminus of the protein. Importantly, one of these truncations leads to ∼80% downregulation of CENP-F expression. We observe that, despite the phenotypes apparent in cultured cells, mutant mice develop normally. Taken together, these mice will serve as important models to study CENP-F biology at organismal level. In addition, because truncations of CENP-F in humans cause a lethal disease termed Strømme syndrome and because CENP-F is involved in cancer development, they might also be relevant disease models.

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Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer

Cited by 38 publications

References 31 publications

Upregulation of centromere protein F is linked to aggressive prostate cancers

Upregulation of centromere protein F is linked to aggressive prostate cancers

HIF-1α promoted vasculogenic mimicry formation in hepatocellular carcinoma through LOXL2 up-regulation in hypoxic tumor microenvironment

Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminal domain are dispensable for normal development in mice

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