Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer

Peng, Chunjie; Zhang, Xiaolei; Yu, Hongli; Wu, Donglai; Zheng, Junhua

doi:10.1097/igc.0b013e31820aaadb

Cited by 66 publications

(51 citation statements)

References 21 publications

(15 reference statements)

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“…Interestingly, it has recently been shown that MEST is a negative regulator of the Wnt pathway and that MEST knockdown might activate Wnt signalling (Jung et al, 2011). Epigenetic regulation of Wnt pathway genes has previously been shown to be associated with patient survival following platinum-based chemotherapy and chemoresistance in ovarian cancer Peng et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling

et al. 2012

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Multiple DNA methylation changes in the cancer methylome are associated with the acquisition of drug resistance; however it remains uncertain how many represent critical DNA methylation drivers of chemoresistance. Using isogenic, cisplatin-sensitive/resistant ovarian cancer cell lines and inducing resensitizaton with demethylating agents, we aimed to identify consistent methylation and expression changes associated with chemoresistance. Using genome-wide DNA methylation profiling across 27 578 CpG sites, we identified loci at 4092 genes becoming hypermethylated in chemoresistant A2780/cp70 compared with the parental-sensitive A2780 cell line. Hypermethylation at gene promoter regions is often associated with transcriptional silencing; however, expression of only 245 of these hypermethylated genes becomes downregulated in A2780/cp70 as measured by microarray expression profiling. Treatment of A2780/ cp70 with the demethylating agent 2-deoxy-5 0 -azacytidine induces resensitization to cisplatin and re-expression of 41 of the downregulated genes. A total of 13/41 genes were consistently hypermethylated in further independent cisplatin-resistant A2780 cell derivatives. CpG sites at 9 of the 13 genes (ARHGDIB, ARMCX2, COL1A, FLNA, FLNC, MEST, MLH1, NTS and PSMB9) acquired methylation in ovarian tumours at relapse following chemotherapy or chemoresistant cell lines derived at the time of patient relapse. Furthermore, 5/13 genes (ARMCX2, COL1A1, MDK, MEST and MLH1) acquired methylation in drug-resistant ovarian cancersustaining (side population) cells. MLH1 has a direct role in conferring cisplatin sensitivity when reintroduced into cells in vitro. This combined genomics approach has identified further potential key drivers of chemoresistance whose expression is silenced by DNA methylation that should be further evaluated as clinical biomarkers of drug resistance.

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Section: Discussionmentioning

confidence: 99%

Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling

et al. 2012

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“…Several studies have suggested that the activation of WNT signaling induces drug resistance in various cancers, including ovarian, colon and pancreatic cancer [98][99][100] ( Figure 2). For example, WNT5A was upregulated in oxaliplatin-resistant ovarian carcinoma cell line.…”

Section: Wnt Signaling In Therapeutic Resistancementioning

confidence: 99%

WNT signaling in glioblastoma and therapeutic opportunities

Lee

Ahn

et al. 2016

Laboratory Investigation

225

182

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WNTs and their downstream effectors regulate proliferation, death, and migration and cell fate decision. Deregulation of WNT signaling is associated with various cancers including GBM, which is the most malignant primary brain cancer. In this review, we will summarize the experimental evidence supporting oncogenic roles of WNT signaling in GBM and discuss current progress in the targeting of WNT signaling as an anti-cancer approach. In particular, we will focus on (1) genetic and epigenetic alterations that lead to aberrant WNT pathway activation in GBM, (2) WNT-mediated control of GBM stem cell maintenance and invasion, and (3) cross-talk between WNT and other signaling pathways in GBM. We will then review the discovery of agents that can inhibit WNT signaling in preclinical models and the current status of human clinical trials.

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“…It has been also found recently that high levels of Wnt5a expression were associated with FIGO stage and a poorer overall survival and progression-free survival compared with low Wnt5a expression [140]. Similarly, positive NAC1 expression significantly correlated with shorter disease-free and overall survival and revealed as an independent prognostic factor for these characteristics after standard platinum-taxane chemotherapy in another recent study [141].…”

Section: Cd24mentioning

confidence: 80%

Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease

Záveský

Jancárková²,

Kohoutová³

2011

neo

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Ovarian cancer representing the most lethal gynecologic malignancy escapes from the efforts to manage the disease. We reviewed the current state of the research considering three main concepts on origin of ovarian cancer including epithelialmesenchymal transition, secondary origin from Müllerian system and cancer stem cell hypothesis. Cytogenetic and molecular characteristics of ovarian cancer are focused particularly on microRNA expression studies revealing huge potential in recent years, although other transcriptomic, proteomic, epigenetic, epidemiologic and immunological factors are touched upon, too. Routine and investigated diagnostic and treatment methods are outlined and several factors revealed to be associated with prognosis of the disease. Despite the huge progress on elucidating factors involved in ovarian cancer carcinogenesis, still remains urgent need to improve both the diagnostics as well as the treatment.

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Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer

Abstract: Wnt5a immunoreactivity may be a useful prognostic indicator in patients with ovarian cancer. These results clarified for the first time the possibility that Wnt5a plays an important role in regulating chemosensitivity to anticancer drugs in ovarian cancer cells.

Cited by 66 publications

References 21 publications

Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling

Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling

WNT signaling in glioblastoma and therapeutic opportunities

Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease

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