Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer

Seabra, Mariana Ataydes Leite; Cândido, Eduardo Batista; Vidigal, Paula Vieira Teixeira; Lamaita, Rívia Mara; Rodrigues, Angelica Nogueira; Filho, Agnaldo Lopes da Silva

doi:10.1055/s-0037-1618597

Cited by 8 publications

(11 citation statements)

References 38 publications

(39 reference statements)

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“…Considering that WWOX is located in FRA16D (a genomic instability hot spot prone to breakage causing germline and somatic copy number variations), 63 this gene is a frequent target for deletions in cancer. Esophageal, 64 colon, 65 stomach, 66 bladder, 35 and uterine cancers 34 are commonly affected by WWOX deep focal deletions, whose occurrence significantly correlates with various pathological and clinical features. 67 Despite the knowledge of WWOX gene function in many cancers, data on brain tumors are limited.…”

Section: Brain Cancersmentioning

confidence: 99%

“…26 Up to date, disturbances in WWOX expression have been associated with cholesterol level disorders, 27,28 type 2 diabetes, 29 spinal-cerebellar ataxia and childhood encephalopathy, 30 and various types of cancer. 5,13,[31][32][33][34][35][36] WWOX has been found to play a crucial role in the differentiation of the skeletal system, mammary gland, and testicles. [37][38][39][40] Growing evidence suggests that it has also a considerable influence on the development of the central nervous system (CNS).…”

Section: Impact Statementmentioning

confidence: 99%

“…Up to date, disturbances in WWOX expression have been associated with cholesterol level disorders, 27 , 28 type 2 diabetes, 29 spinal-cerebellar ataxia and childhood encephalopathy, 30 and various types of cancer. 5 , 13 , 31 – 36 …”

Section: Introductionmentioning

confidence: 99%

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The WWOX gene in brain development and pathology

Kośla

Kałuzińska

2020

Exp Biol Med (Maywood)

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Shortly after its discovery in 2000, WWOX was hailed as a tumor suppressor gene. In subsequent years of research, this function was confirmed indisputably. Majority of tumors show high rate of loss of heterozygosity and decreased expression of WWOX. Nevertheless, over the years, the range of its known functions, at the cellular, organ and system levels, has expanded to include metabolism and endocrine system control and CNS differentiation and functioning. Despite of its function as a tumor suppressor gene, WWOX genetic alternations were found in a number of metabolic and neural diseases. A lack of WWOX protein as a consequence of germline mutations results in brain development disturbances and malfunctions. Impact statement WW domain-containing oxidoreductase encoded by the WWOX gene is a transcription regulator and a key player in a number of cellular and biological processes such as tumor suppression, cell proliferation, apoptosis induction, steroid metabolism, and central nervous system development. This review provides a comprehensive summary of currently known roles and discusses the importance of WWOX gene for CNS development and functioning.

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Section: Brain Cancersmentioning

confidence: 99%

Section: Impact Statementmentioning

confidence: 99%

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The WWOX gene in brain development and pathology

Kośla

Kałuzińska

2020

Exp Biol Med (Maywood)

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“…In addition to steroid-hormone regulated tissues like those in the testis, ovary and breast, the WWOX gene also shows high expression in the brain and cerebellum (Nunez et al, 2006). Loss of correct WWOX expression is a common event associated with cancer promotion, progression and resistance to treatment (Płuciennik et al, 2006, 2014; Dias et al, 2007; Donati et al, 2007; Wang et al, 2011; Lan et al, 2012; Sun et al, 2017; Seabra et al, 2018). Unlike classic suppressor genes, the loss of functionality of only one WWOX allele is sufficient to increase the chance of cancerogenesis (haploinsufficiency).…”

Section: Introductionmentioning

confidence: 99%

The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells

Kośla

Płuciennik

Styczeń-Binkowska

et al. 2019

Front. Cell. Neurosci.

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The brain is the most functionally organized structure of all organs. It manages behavior, perception and higher cognitive functions. The WWOX gene is non-classical tumor suppressor gene, which has been shown to have an impact on proliferation, apoptosis and migration processes. Moreover, genetic aberrations in WWOX induce severe neuropathological phenotypes in humans and rodents. The aim of the present study was to investigate in detail the impact of WWOX on human neural progenitor cell (hNPC) maintenance and how depletion of WWOX disturbs signaling pathways playing a pivotal role in neuronal differentiation and central nervous system (CNS) organogenesis. hNPC with a silenced WWOX gene exhibited lowered mitochondrial redox potential, enhanced adhesion to fibronectin and extracellular matrix protein mixture, downregulation of MMP2/9 expression and impaired 3D growth. Global transcriptome analysis using cap analysis of gene expression (CAGE) found that WWOX downregulation significantly changes the expression of multiple genes engaged in cytoskeleton organization, adhesion, cell signaling and chromatin remodeling. The massive changes in gene expression caused by WWOX silencing may strongly affect the differentiation and migration of neurons in organogenesis, brain injury, cancerogenesis or neurodifferentiation. WWOX gene appears to be an important regulator of neural tissue architecture and function.

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“…Qu et al showed that WWOX expression is reduced in human cervical cancer and cervical cancer cell lines 25 . WWOX expression has been reported to be involved in the regulation of cell cycle, apoptosis, angiogenesis and tumorigenesis 26 - 28 . Reconstruction of WWOX in HeLa cervical cancer cells inhibited cell proliferation and triggered apoptosis, while knockdown of WWOX in SiHa cells enhanced cell proliferation and inhibited apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Relationship of genetic variant distributions of WW domain-containing oxidoreductase gene with uterine cervical cancer

Lin

Hsiao

et al. 2018

Int. J. Med. Sci.

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To our knowledge, no study investigates the association of genetic variant distributions of WW domain-containing oxidoreductase (WWOX) gene with development of invasive cancer, clinicopathologic variables and patient survival in uterine cervical cancer for Taiwanese women. We therefore conducted this study to explore the clinical involvements of WWOX single nucleotide polymorphisms (SNPs) in cervical cancer. One hundred and thirty-one patients with cervical invasive cancer and 93 patients with precancerous lesions as well as 316 control women were consecutively enrolled. The genotypic frequencies of WWOX genetic variants rs73569323, rs383362, rs11545028, rs3764340 and rs12918952 were determined by real-time polymerase chain reaction. The results revealed that only WWOX SNP rs3764340 was associated between patients with cervical invasive cancer and normal controls among 5 WWOX genetic variants. Cervical cancer patients with genotypes GA/AA in WWOX SNP rs12918952 were associated with parametrium invasion and pelvic lymph node metastasis. Univariate analysis found that WWOX SNPs rs73569323 and rs11545028 were associated with patient survival, whereas multivariate analysis revealed CT/TT in rs11545028 was the only genetic variant, which could predict better overall survival, among 5 WWOX SNPs in Taiwan. In conclusion, Taiwanese women with CG/GG in WWOX SNP rs3764340 are susceptible to cervical invasive cancer. Cervical cancer patients with GA/AA in rs12918952 tend to have more risk to develop parametrium invasion and pelvic lymph node metastasis. Among 5 WWOX SNPs, rs11545028 is the only genetic variant associated with patient survival, in which CT/TT could predict better overall survival in Taiwanese women.

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Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer

Cited by 8 publications

References 38 publications

The WWOX gene in brain development and pathology

The WWOX gene in brain development and pathology

The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells

Relationship of genetic variant distributions of WW domain-containing oxidoreductase gene with uterine cervical cancer

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