Wnt inhibitory factor-1 regulates glioblastoma cell cycle and proliferation

Wu, Jun; Jia-sheng, Fang; Yang, Zhiyong; Chen, Fenghua; Liu, Jingfang; Wang, Yanjin

doi:10.1016/j.jocn.2011.12.023

Cited by 33 publications

(23 citation statements)

References 15 publications

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“…Cytoplasmic staining of WIF1 was confirmed as positive according to the previous reports [20–22] and the recommendation of the antibody production company (Abcam, ab71205) and that of SFRP1 was confirmed according to the previous reports [23, 24] and the recommendation of the antibody production company (Abcam, ab4193). The intensity of cytoplasmic staining was scored from 0 to 4+ (0: negative; 1+: weak; 2+: mild; 3+: moderate; and 4+: intense staining).…”

Section: Methodsmentioning

confidence: 54%

Coexpression of SFRP1 and WIF1 as a Prognostic Predictor of Favorable Outcomes in Patients with Colorectal Carcinoma

Huang

Zhong

Gao

et al. 2014

BioMed Research International

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Colorectal tumorigenesis is ascribed to the activity of Wnt signaling pathway in a ligand-independent manner mainly through APC and CTNNB1 gene mutations and in a ligand-dependent manner through low expression of Wnt inhibitors such as WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 1 (SFRP1). In this study we found that WIF1 protein expression was increased and SFRP1 was decreased significantly in CRC tissue versus normal tissue, and high expression of WIF1 was associated with big tumor diameters and deep invasion, and loss of SFRP1 expression was associated with the left lesion site, deep invasion, and high TNM stage. Among the four expression patterns (WIF+/SFRP1+, WIF+/SFRP1−, WIF−/SFRP1+, and WIF−/SFRP1−) only coexpression of WIF1 and SFRP1 (WIF+/SFRP1+) was associated with favorable overall survival, together with low TNM stage, as an independent prognostic factor as shown in a multivariate survival model. The results indicated that WIF1 seemed to play an oncogenic role, while SFRP1 seemed to play an oncosuppressive role although both of them are secreted Wnt antagonists. Coexpression of SFRP1 and WIF1, rather than SFRP1 or WIF1 alone, could be used, together with low TNM stage, as a prognostic predictor of favorable outcomes in CRC.

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Section: Methodsmentioning

confidence: 54%

Coexpression of SFRP1 and WIF1 as a Prognostic Predictor of Favorable Outcomes in Patients with Colorectal Carcinoma

Huang

Zhong

Gao

et al. 2014

BioMed Research International

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“…There are also genes participating in immune response. WIF1 is a gene what is involved in different malignancies and it regulates cell cycle [18,19]. In recent study its involvement in osteosarcoma was shown [20].…”

Section: Identification Of Differentially Expressed Genes Between Normentioning

confidence: 99%

Transcriptome analysis of osteosarcoma identifies suppression of wnt pathway and up-regulation of adiponectin as potential biomarker

Märtson¹,

Kõks²,

Reimann³

et al. 2013

Genomics Discov

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Osteosarcoma (OS) is primary malignant bone tumour with complicated early diagnosis. There are no specific markers currently available for predicting the prognosis and chemosensitivity of OS. In present study we performed transcriptome profiling of single patient tumour tissue with RNA-seq technology. We analysed surgically removed sarcoma sample from single 16 years old male patient. Transciptome analysis was done with RNA-seq technology, bioinformatics with Lifescope and R Bioconductor. Validation experiments were done with quantitative real-time PCR (QRTPCR). After quality and coverage filtering, RNA-seq experiment resulted 29,311,899 mapped reads for sarcoma and 22,099,159 mapped reads for normal bone tissue. 65 genes were differentially expressed with FDR corrected statistical significance below 0.05. Seven genes were down-regulated and 58 genes were up-regulated in sarcoma. The most highly up-regulated gene in sarcoma was adiponectin, ADIPOQ (with adjusted p-value 5.5E-07, log2 fold change was 7.9). Many of the genes we found are related to the adipose tissue metabolism (ADIPOQ, PLIN1, FABP4) and to the Wnt signalling suppression (WIF1, SOST). We also found novel fusion transcript between the genes LMTK2 and ZSWIM5. LMTK2 is lemur tyrosine kinase 2, and it has been shown to be involved in NGF-TrkA signalling. Interestingly, studies support the involvement of LMTK2 in development of prostate cancer. ZSWIM5 is zinc finger SWIM domain protein 5 and its function is not known. Immunohistochemical analysis confirmed positive staining for adiponectin in osteosarcoma. This paper is a good illustration how transcriptome analysis can find new biomarkers and targets for complex diseases.

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“…WIF-1 silencing correlates with its hypermethylation in NSCLC. Furthermore, WIF-1 silencing may be an early epigenetically carcinogenic event and plays a significant role in tumor development and progression [8]. Our results suggest that WIF-1 can act as a negative feedback regulator of Wnt signal pathway via promoter demethylation of WIF-1.…”

Section: Discussionmentioning

confidence: 66%

“…Wnt antagonists, including the secreted frizzled-related protein (SFRP) family, Wnt inhibitory factor-1 (WIF-1) and cerberus, combine with Wnt molecules directly to inhibit Wnt signal pathway. Silence of WIF-1, along with hypermethylation, has been observed in some tumors [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer

Xie

Zhang

et al. 2015

Med Oncol

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Wingless-type (Wnt) family of secreted glycoproteins is a group of signal molecules implicated in oncogenesis. Abnormal activation of Wnt signal pathway is associated with a variety of human cancers, including non-small cell lung cancer (NSCLC). Wnt antagonists, such as the secreted frizzled-related protein (SFRP) family, Wnt inhibitory factor-1 (WIF-1) and cerberus, inhibit Wnt signal pathway by directly binding to Wnt molecules. Norcantharidin (NCTD) is known to possess anticancer activity but less nephrotoxicity than cantharidin. In this study, we found that NCTD inhibited cell proliferation, induced apoptosis, arrested cell cycle and suppressed cell invasion/migration in vitro. Additionally, Wnt signal pathway transcription was also suppressed. NCTD treatment blocked cytoplasmic translocation of beta-catenin into the nucleus. Alterations of apoptosis-related proteins, such as Bax, cleaved caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic), had been detected. Furthermore, the expression levels of WIF-1 and SFRP1 were significantly increased in NCTD-treated groups compared with negative control (NC) groups. Abnormal methylation was observed in NC groups, while NCTD treatment promoted WIF-1 demethylation. The present study revealed that NCTD activated WIF-1 via promoter demethylation, inhibiting the canonical Wnt signal pathway in NSCLC, which may present a new therapeutic target in vivo.

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Wnt inhibitory factor-1 regulates glioblastoma cell cycle and proliferation

Cited by 33 publications

References 15 publications

Coexpression of SFRP1 and WIF1 as a Prognostic Predictor of Favorable Outcomes in Patients with Colorectal Carcinoma

Coexpression of SFRP1 and WIF1 as a Prognostic Predictor of Favorable Outcomes in Patients with Colorectal Carcinoma

Transcriptome analysis of osteosarcoma identifies suppression of wnt pathway and up-regulation of adiponectin as potential biomarker

Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer

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