Reduced expression of cenp-e in human hepatocellular carcinoma

Liu, Zi-jie; Liu, Kang; Wu, Xia; Cao, Ju; Liu, Bin; Li, Su-Yan; Si, Qiong; Cai, Yan; Chang, Yan; Zhang, Yan; Weng, Yaguang

doi:10.1186/1756-9966-28-156

Cited by 26 publications

(20 citation statements)

References 30 publications

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“…These results are consistent with those of a previous study in which the silenced expression of KIF14 in pancreatic cancer cells resulted in increased anchorage-independent survival [43]. Apart from KIF14, many other cytokinesis regulators have also been reported as tumor suppressor genes, including KIF1A, KIF1B, KIF3, KIF4, KIF10, Von Hippel-Lindau syndrome protein (pVHL) and BRCA2 [16]–[18], [44]–[47]. Taken together, these results suggest that a KIF14 deficiency might promote aneuploidy, resulting in tumor formation, and that KIF14 might act as a tumor suppressor in lung cancer.…”

Section: Discussionsupporting

confidence: 92%

“…Many components that regulate cytokinesis have been identified, and some molecules, including KIFs, have been clearly associated with cancer. For example, KIF2 and KIF15 have been identified as tumor antigens in breast cancer [12], [13]; KIF13A is overexpressed in some retinoblastomas [14]; KIF20A is up-regulated in pancreatic cancer [15]; KIF3 and KIF4 have been identified as tumor suppresser genes in gastric cancer [16], [17]; and the expression of KIF10 is reduced in hepatocellular carcinoma [18]. In addition, it has been reported that some KIF family members, including KIF3, KIF4 and KIF22, have conflicting roles in tumorigenesis [16], [17], [19]–[23].…”

Section: Introductionmentioning

confidence: 99%

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The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma

et al. 2013

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The motor protein kinesin superfamily proteins (KIFs) are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively), and the protein levels were also inversely correlated with metastasis (P<0.0001). The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11) and melanoma cell adhesion molecule (MCAM) as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma

et al. 2013

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“…Moreover, CENP-E expression negatively correlated with disease-specific survival in patients with breast cancer [423]. In contrast, human hepatocellular carcinoma exhibits abnormally low levels of CENP-E [424]. Several non-synonymous single nucleotide polymorphisms were also reported in CENP-E and the Y63H point mutation, which disrupts the native conformation of the ATP-binding region in the CENP-E motor domain, was found to be associated with cancer [425].…”

Section: Consequences Of Abnormal Congressionmentioning

confidence: 99%

Mechanisms of Chromosome Congression during Mitosis

Maiato

Gomes

Sousa

et al. 2017

Biology

159

176

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Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E) that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle microtubule diversity by means of tubulin post-translational modifications. This so-called “tubulin code” might work as a navigation system that selectively guides kinetochore motors with opposite polarities along specific spindle microtubule populations, ultimately leading to the congression of peripheral chromosomes. We propose an integrated model of chromosome congression in mammalian cells that depends essentially on the following parameters: (1) chromosome position relative to the spindle poles after nuclear envelope breakdown; (2) establishment of stable end-on kinetochore-microtubule attachments and bi-orientation; (3) coordination between kinetochore- and arm-associated motors; and (4) spatial signatures associated with post-translational modifications of specific spindle microtubule populations. The physiological consequences of abnormal chromosome congression, as well as the therapeutic potential of inhibiting chromosome congression are also discussed.

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“…Microinjection of a CENP-E monoclonal antibody during prometaphase significantly delayed the onset of anaphase [18]. The reduced expression level of CENP-E has been observed in human hepatocellular carcinoma cases [19]. Here the expression level of CENP-E in human hepatic cell line L02 was higher than that in human hepatoma carcinoma cell line HepG2 during cell division phase suggesting the role in anti-tumour activity.…”

Section: Introductionmentioning

confidence: 81%