<i>WWOX</i> Gene Expression Abolishes Ovarian Cancer Tumorigenicity <i>In vivo</i> and Decreases Attachment to Fibronectin via Integrin α3

Gourley, Charlie; Paige, Adam J.W.; Taylor, Karen; Ward, Carol; Kuske, Barbara; Zhang, Jieqing; Sun, Mingjun; Janczar, Szymon; Harrison, David J.; Muir, Morwenna; Smyth, John F.; Gabra, Hani

doi:10.1158/0008-5472.can-08-2974

Cited by 89 publications

(104 citation statements)

References 43 publications

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“…WWOX-transfected PEO1 cells showed a decrease in the adhesion to fibronectin in comparison to vector-transfected control cells, which suggests a WWOX influence on processes such as tumor invasiveness and spread (40). Gourley et al also confirmed these results on the ovarian cancer cell line, A2780, and showed that WWOX overexpression reduces adhesion through membranous integrin α3 protein (22).…”

Section: Discussionmentioning

confidence: 77%

“…Experiments performed by Gourley et al on ovarian cancer cells confirmed that WWOX protein is an inhibitor of anchorage-independent growth also in this case. Moreover, WWOX silencing was found to result in enhanced adhesion to fibronectin (22).…”

Section: Introductionmentioning

confidence: 97%

“…However, the results of a test of growth in Matrigel showed that the transduced cells had more 'normal' phenotype and formed mammary ducts. Control cells in Matrigel grew into spherical structures, typical of neoplastic cells (22). The improved differentiation evident in cells with an elevated WWOX level suggests its involvement in these type of processes.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, Gourley et al identified its role in the decrease of integrin activity and adhesion of tumor cells to fibronectin (22).…”

Section: Introductionmentioning

confidence: 99%

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The WWOX tumor suppressor gene in endometrial adenocarcinoma

Płuciennik

Kośla

Wójcik‐Krowiranda

et al. 2013

International Journal of Molecular Medicine

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Abstract. Endometrial cancer is a lethal malignancy, the causes of which remain to be determined. The aim of the present study, carried out on tumor samples from 79 patients, was to evaluate the role of the WWOX tumor suppressor gene in endometrial adenocarcinoma. The expression levels of WWOX and its protein content were assessed in normal endometrium and cancer samples. Quantitative PCR was used to assess the correlation between the expression levels of WWOX and the genes involved in the proliferation (MKI67), apoptosis (BAX, BCL2), signal transduction (EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription regulation (TP73, NCOR1). The relationship between loss of hetero zygosity (LOH) and WWOX mRNA levels was also investigated using high resolution melting. Results of the present study demonstrated a positive correlation of WWOX expression with BCL2 and CCND1 and a negative correlation with BAX, CDH1, NCOR1 and BCL2/BAX ratio. The results also showed that loss of heterozygosity at two analyzed loci of the WWOX gene is frequent in patients with endometrial cancer and that WWOX expression levels are lower in tumor samples than in normal tissue. In conclusion, WWOX may be involved in endometrial cancer.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

“…Moreover, Gourley et al identified its role in the decrease of integrin activity and adhesion of tumor cells to fibronectin (22).…”

Section: Introductionmentioning

confidence: 99%

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The WWOX tumor suppressor gene in endometrial adenocarcinoma

Płuciennik

Kośla

Wójcik‐Krowiranda

et al. 2013

International Journal of Molecular Medicine

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“…Bednarek et al (1,25) first reported that ectopic expression of WWOX could inhibit breast cancer viability both in vitro and in vivo. Gourley et al (26) revealed that WWOX expression abolishes ovarian cancer tumorigenicity in vivo, and Fabbri et al (10) also found an increase of WWOX in lung cancer cells exhibits marked suppression of tumorigenicity. Recent publications demonstrated that ectopic expression of WWOX leads to cell apoptosis in tumors such as lung cancer, glioblastoma multiforme, hepatoma, ovarian and prostate cancer as well (17,19,24,27,28).…”

Section: Discussionmentioning

confidence: 99%

The role of the WWOX gene in leukemia and its mechanisms of action

et al. 2013

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Abstract. The WW domain-containing oxidoreductase (WWOX) gene which encompasses the common human fragile site FRA16D has been proposed as a putative tumor suppressor gene, and loss of WWOX expression has been found in several types of solid cancer. As the role of WWOX in human leukemia has not yet been fully elucidated, the present study examined the expression of WWOX in patients with different types of leukemia as well as in leukemia-derived cell lines. Based on the data, WWOX mRNA (WWOX) and protein (Wwox) were significantly reduced or absent in the leukemia patients as well as in the cell lines. In addition, a recombinant expression vector, pGC-FU-WWOX, was constructed and transfected WWOX cDNA into Jurkat cells (acute T-lymphoblastic leukemia) and K562 cells (chronic myeloid leukemia in erythroid crisis) which all lack endogenous Wwox. In vitro experiments indicated that restoration of Wwox in Jurkat and K562 cells significantly suppressed proliferation and colony formation. Of note, apoptosis was also induced by Wwox restoration. Furthermore, we traced the mechanisms underlying this process and found that Wwox restoration could trigger the mitochondrial pathway in leukemia. Our data provide evidence that WWOX exerts a role as a tumor suppressor gene in leukemia, possibly by inhibiting proliferation and promoting apoptosis via the mitochondrial pathway.

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WWOX: Its genomics, partners, and functions

Mare¹,

Salah²,

Aqeilan³

2009

J of Cellular Biochemistry

130

156

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The WW domain-containing oxidoreductase (WWOX) spans one of the most active common fragile sites (CFSs) involved in cancer, FRA16D. WWOX encodes a 46-kDa protein that contains two N-terminal WW domains and a central short-chain dehydrogenase/reductase (SDR) domain. Through its WW domain, Wwox interacts with its partners and modulates their functions. Our data indicate that Wwox suppresses the transactivation function of several transcription factors implied in neoplasia by sequestering them in the cytoplasm. Work from our laboratory and other research groups have demonstrated that Wwox participates in a number of cellular processes including growth, differentiation, apoptosis, and tumor suppression. Targeted deletion of the Wwox gene in mice causes increased spontaneous and chemically induced tumor incidence supporting bona fide tumor suppressor function of WWOX. Moreover, generation of the Wwox-deficient mice uncovers, at least in part, some of the physiological in vivo functions of the WWOX gene. This review focuses on recent progress that elucidates Wwox functions in biology and pathology.

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WWOX Gene Expression Abolishes Ovarian Cancer Tumorigenicity In vivo and Decreases Attachment to Fibronectin via Integrin α3

Cited by 89 publications

References 43 publications

The WWOX tumor suppressor gene in endometrial adenocarcinoma

The WWOX tumor suppressor gene in endometrial adenocarcinoma

The role of the WWOX gene in leukemia and its mechanisms of action

WWOX: Its genomics, partners, and functions

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