Beyond cytokinesis: the emerging roles of CEP55 in tumorigenesis

Jeffery, Jessie; Sinha, Debottam; Srihari, Sriganesh; Kalimutho, Murugan; Khanna, Kum Kum

doi:10.1038/onc.2015.128

Cited by 119 publications

(133 citation statements)

References 85 publications

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“…Through the combined application of homozygosity mapping and exome sequencing, we identified the likely causative genetic defect, a nonsense mutation in CEP55 (c.1274C>A; p.S425X), which encodes centrosomal protein-55 kDa (CEP55). Although not implicated previously in any genetic disorder, CEP55 is known to be essential for the final step of cytokinesis, abscission and has also been found to be upregulated in some tumours 5. More recently, loss of cep55l, the zebrafish ortholog of CEP55 , was also shown to result in various developmental defects in zebrafish embryos 6.…”

Section: Introductionmentioning

confidence: 99%

A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis

et al. 2017

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BackgroundHydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. The goals of this work are to describe a novel autosomal-recessive syndrome that includes hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH)); to identify its genetic cause(s) and to provide functional insight into pathomechanism.MethodsWe used homozygosity mapping and exome sequencing to identify recessive mutations in a single family with three affected fetuses. Immunohistochemistry, RT-PCR and imaging in cell lines, and zebrafish models, were used to explore the function of the gene and the effect of the mutation.ResultsWe identified a homozygous nonsense mutation in CEP55 segregating with MARCH. Testing the effect of this allele on patient-derived cells indicated both a reduction of the overall CEP55 message and the production of a message that likely gives rise to a truncated protein. Suppression or ablation of cep55l in zebrafish embryos recapitulated key features of MARCH, most notably renal dysplasia, cerebellar hypoplasia and craniofacial abnormalities. These phenotypes could be rescued by full-length but not truncated human CEP55 message. Finally, we expressed the truncated form of CEP55 in human cells, where we observed a failure of truncated protein to localise to the midbody, leading to abscission failure and multinucleated daughter cells.Conclusions CEP55 loss of function mutations likely underlie MARCH, a novel multiple congenital anomaly syndrome. This association expands the involvement of centrosomal proteins in human genetic disorders by highlighting a role in midbody function.

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Section: Introductionmentioning

confidence: 99%

A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis

et al. 2017

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“…Accumulating evidences have shown CEP55 is highly expressed in several cancers including human colon cancer and lung cancer (7)(8)(9)(10). Interestingly, CEP55 has been demonstrated to be involved in tumorigenesis of breast cancer (11)(12)(13). However, the functional role of CEP55 in breast cancer is still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Lentivirus-mediated knockdown of CEP55 suppresses cell proliferation of breast cancer cells

Wang

Jin

Dai

et al. 2016

BST

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“…Soon after, overexpression of CEP55 was found in lung adenocarcinoma, gastric carcinoma and hepatocellular carcinoma, where it promote cell proliferation and invasion (17,21,22). It was among the top 70 most highly overexpressed genes in an analysis across 12 cancer types including lung, lymphoma, medulloblastoma and breast, and was identified in prognostic signatures for these cancers (18,23). In this study, we found that CEP55 expression increased significantly in glioma and GBM U251 cells than in normal brain tissue.…”

Section: Discussionmentioning

confidence: 58%

“…CEP55 is a conserved gene to preventing genetic damage and its protein acts as a regulator of cell cycle progression ensuring proper abscission, the final stage of cytokinesis (18). Therefore, the expression of CEP55 might be regulated by other driver gene.…”

Section: Egfrviii Promoted the Proliferation And Expression Of Cep55 mentioning

confidence: 99%

Overexpression of centrosomal protein 55 regulates the proliferation of glioma cell and mediates proliferation promoted by EGFRvIII in glioblastoma U251 cells

et al. 2017

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Abstract. The epidermal growth factor receptor (EGFR) is often amplified in glioma, with the most common extracellular domain mutation being EGFR variant III (EGFRvIII). Abnormal EGFRvIII signaling has been shown to be important in driving tumor progression. Centrosomal protein 55 (CEP55), a member of the centrosomal relative proteins family, participates cytokinesis in the cell cycle. It exists in a few normal tissues and various tumor cells. The expression and function of CEP55 in human glioma cells need to investigate. In this study, the expression of CEP55 was detected in 40 cases of glioma tissues and 10 cases of non-tumor brain tissue. The proliferation of glioblastoma U251 cells was analyzed after transfection with EGFRvIII and CEP55 siRNA. We found that the expression of CEP55 was increased significantly in the glioma tissues than in normal brain tissue. The proliferation of U251 cells increased remarkably after transfection with EGFRvIII. Knockdown of CEP55 inhibited proliferation of U251 cells and was able to eliminate the effect of promoting proliferation induced by EGFRvIII in U251 cells. CEP55 played a key role in the proliferation of glioma cells and mediated EGFRvIII-stimulated proliferation in glioma cells. CEP55 might be a novel molecular therapeutic target in patients with gliomas expressing EGFRvIII.

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Beyond cytokinesis: the emerging roles of CEP55 in tumorigenesis

Cited by 119 publications

References 85 publications

A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis

A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis

Lentivirus-mediated knockdown of CEP55 suppresses cell proliferation of breast cancer cells

Overexpression of centrosomal protein 55 regulates the proliferation of glioma cell and mediates proliferation promoted by EGFRvIII in glioblastoma U251 cells

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