Expression of the Actin-binding Proteins Indicates that Cofilin and Fascin are Related to Breast Tumour Size

Zhang, Y; Tong, Xiao

doi:10.1177/147323001003800331

Cited by 24 publications

(19 citation statements)

References 27 publications

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“…Specifically, we observed the down-regulation of the ACTN4 gene, which was also confirmed by the proteomic analysis. Even though the roles of ACTN4 in tumors reported in the literature are contradictory [29], [30] our data are in agreement with those of authors who demonstrated the role of ACTN4 gene in suppressing tumorigenicity in different tumor types [31]–[33]. Additionally, our data, showing the increase of some members of the 14-3-3 protein family, are in agreement with those of other authors, who demonstrated a positive role of such proteins in the induction of oncogenic transformation and in promoting cancer cell survival [34], [35].…”

Section: Discussionsupporting

confidence: 91%

LMNA Knock-Down Affects Differentiation and Progression of Human Neuroblastoma Cells

et al. 2012

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BackgroundNeuroblastoma (NB) is one of the most aggressive tumors that occur in childhood. Although genes, such as MYCN, have been shown to be involved in the aggressiveness of the disease, the identification of new biological markers is still desirable. The induction of differentiation is one of the strategies used in the treatment of neuroblastoma. A-type lamins are components of the nuclear lamina and are involved in differentiation. We studied the role of Lamin A/C in the differentiation and progression of neuroblastoma.Methodology/Principal FindingsKnock-down of Lamin A/C (LMNA-KD) in neuroblastoma cells blocked retinoic acid-induced differentiation, preventing neurites outgrowth and the expression of neural markers. The genome-wide gene-expression profile and the proteomic analysis of LMNA-KD cells confirmed the inhibition of differentiation and demonstrated an increase of aggressiveness-related genes and molecules resulting in augmented migration/invasion, and increasing the drug resistance of the cells. The more aggressive phenotype acquired by LMNA-KD cells was also maintained in vivo after injection into nude mice. A preliminary immunohistochemistry analysis of Lamin A/C expression in nine primary stages human NB indicated that this protein is poorly expressed in most of these cases.Conclusions/SignificanceWe demonstrated for the first time in neuroblastoma cells that Lamin A/C plays a central role in the differentiation, and that the loss of this protein gave rise to a more aggressive tumor phenotype.

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Section: Discussionsupporting

confidence: 91%

LMNA Knock-Down Affects Differentiation and Progression of Human Neuroblastoma Cells

et al. 2012

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“…We believe that these candidates are enriched in true positive results with a higher chance of experimental validation, but would have been overlooked if we had only considered individual gene associations, given their modest associations with breast cancer. This list supports previously well-studied breast cancer genes, such as the BRCA1 (breast cancer breast cancer 1, early onset) associated RING (really interesting new gene) domain 1 gene ( BARD1 ) [60,61], the mucin 1 ( MUC1 ) [62,63] or cofilin-1 genes ( CFL1 ) [64,65], but also suggest novel candidates that warrant further investigation in breast cancer. Some of these novel genes, such as CSNK2A1 , ARHGAP21 and PRKACA have already been somehow implicated (genetic association, differential expression and mutation studies) in others types of cancers, namely neck squamous carcinoma [48], colorectal cancer risk [50], lung squamous cell carcinoma [51] and pituitary tumors [49]; while others, such as PPP2R5A , have not been studied in cancer, but may represent good biological candidates, given the involvement of other members of the known tumor suppressor phosphatase 2A family in ovarian, uterine and breast cancer risk [66,67].…”

Section: Discussionsupporting

confidence: 81%

Hope for GWAS: Relevant Risk Genes Uncovered from GWAS Statistical Noise

Correia

Diekmann

Vicente

et al. 2014

IJMS

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Hundreds of genetic variants have been associated to common diseases through genome-wide association studies (GWAS), yet there are limits to current approaches in detecting true small effect risk variants against a background of false positive findings. Here we addressed the missing heritability problem, aiming to test whether there are indeed risk variants within GWAS statistical noise and to develop a systematic strategy to retrieve these hidden variants. Employing an integrative approach, which combines protein-protein interactions with association data from GWAS for 6 common diseases, we found that associated-genes at less stringent significance levels (p < 0.1) with any of these diseases are functionally connected beyond noise expectation. This functional coherence was used to identify disease-relevant subnetworks, which were shown to be enriched in known genes, outperforming the selection of top GWAS genes. As a proof of principle, we applied this approach to breast cancer, supporting well-known breast cancer genes, while pinpointing novel susceptibility genes for experimental validation. This study reinforces the idea that GWAS are under-analyzed and that missing heritability is rather hidden. It extends the use of protein networks to reveal this missing heritability, thus leveraging the large investment in GWAS that produced so far little tangible gain.

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“…There was also no correlation observed between cofilin expression and tumor size. In contrast, another study demonstrated a positive association between cofilin expression and tumor stages T0, T1, and T2 (but not T3) in breast cancer (39). Resolution of this discrepancy requires additional study.…”

Section: Discussionmentioning

confidence: 87%

Overexpression of cofilin correlates with poor survival in breast cancer: A tissue microarray analysis

et al. 2017

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Cofilin, a key regulator of actin cytoskeleton dynamics, is considered to be involved in cellular migration, tumor invasion and mitosis, and its activity is increased in cancer cells. To address the association between cofilin and breast cancer prognosis, which is unclear at present, cofilin expression was analyzed in tissue microarrays of tumors from 310 patients with breast cancer via immunohistochemistry. In a multivariate Cox regression analysis, a high expression of cofilin in tumor cells correlated significantly with shorter overall survival (hazard ratio, 2.22; 95% confidence interval, 1.35–3.66, P=0.002, and with the Nottingham histologic grade, Ki-67 status and human epidermal growth factor receptor 2 status (P=0.031, 0.001, and 0.001, respectively). Cofilin expression was not observed as correlated with estrogen or progesterone receptor expression, tumor size or lymph node status. These data demonstrate that cofilin is associated with poor outcome, thereby suggesting that it is a potential prognostic factor in breast cancer.

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Expression of the Actin-binding Proteins Indicates that Cofilin and Fascin are Related to Breast Tumour Size

Cited by 24 publications

References 27 publications

LMNA Knock-Down Affects Differentiation and Progression of Human Neuroblastoma Cells

LMNA Knock-Down Affects Differentiation and Progression of Human Neuroblastoma Cells

Hope for GWAS: Relevant Risk Genes Uncovered from GWAS Statistical Noise

Overexpression of cofilin correlates with poor survival in breast cancer: A tissue microarray analysis

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