Tankyrase Promotes Aerobic Glycolysis and Proliferation of Ovarian Cancer through Activation of Wnt/<i>β</i>-Catenin Signaling

Yang, Hongyi; Shen, Jin-Xing; Wang, Yi; Liu, Yu; Shen, Dong‐Yan; Song, Qisheng

doi:10.1155/2019/2686340

Cited by 34 publications

(52 citation statements)

References 33 publications

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“…For example, the Wnt ligand WNT10A activates canonical Wnt signaling in ovarian cancer cell lines leading to increased viability and cell migration [58]. Additionally, the poly(ADP) ribose polymerase (PARP) Tankyrase (TNKS) activates canonical Wnt signaling in ovarian cancer independent of Wnt ligands through destabilization of the destruction complex [49]. In this context, TNKS-activated Wnt/β-catenin signaling contributes to colony formation, migration, invasion, and tumorigenic potential of ovarian cancer cell lines, as well as the promotion of aerobic glycolysis, which is often observed in malignant cells [49].…”

Section: Tumorigenesismentioning

confidence: 99%

“…Additionally, the poly(ADP) ribose polymerase (PARP) Tankyrase (TNKS) activates canonical Wnt signaling in ovarian cancer independent of Wnt ligands through destabilization of the destruction complex [49]. In this context, TNKS-activated Wnt/β-catenin signaling contributes to colony formation, migration, invasion, and tumorigenic potential of ovarian cancer cell lines, as well as the promotion of aerobic glycolysis, which is often observed in malignant cells [49]. Similarly independent of Wnt ligands, RSPO1 promotes ovarian cancer cell survival and migration through upstream activation of the Wnt/β-catenin signaling pathway [59].…”

Section: Tumorigenesismentioning

confidence: 99%

“…Similarly independent of Wnt ligands, RSPO1 promotes ovarian cancer cell survival and migration through upstream activation of the Wnt/β-catenin signaling pathway [59]. When either TNKS or RSPO1 are inhibited, Wnt/β-catenin signaling activity decreases and ovarian cancer cells undergo apoptosis [49,59].…”

Section: Tumorigenesismentioning

confidence: 99%

“…Concerning gynecologic malignancies, CTNNB1 mutations are detected in uterine endometrial, ovarian endometrioid, and ovarian clear cell carcinomas [ 7 , 47 , 48 ]. Hyperactivation of Wnt/β-catenin signaling through these mechanisms are implicated in tumorigenesis, tumor progression, recurrence, and chemoresistance in several cancers, including gynecologic malignancies [ 7 , 8 , 26 , 49 , 50 ].…”

Section: Wnt Signalingmentioning

confidence: 99%

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Wnt Signaling in Gynecologic Malignancies

McMellen¹,

Woodruff²,

Corr

et al. 2020

IJMS

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Gynecologic malignancies, including ovarian cancer, endometrial cancer, and cervical cancer, affect hundreds of thousands of women worldwide every year. Wnt signaling, specifically Wnt/β-catenin signaling, has been found to play an essential role in many oncogenic processes in gynecologic malignancies, including tumorigenesis, metastasis, recurrence, and chemotherapy resistance. As such, the Wnt/β-catenin signaling pathway has the potential to be a target for effective treatment, improving patient outcomes. In this review, we discuss the evidence supporting the importance of the Wnt signaling pathways in the development, progression, and treatment of gynecologic malignancies.

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Section: Tumorigenesismentioning

confidence: 99%

Section: Tumorigenesismentioning

confidence: 99%

Section: Tumorigenesismentioning

confidence: 99%

Section: Wnt Signalingmentioning

confidence: 99%

See 2 more Smart Citations

Wnt Signaling in Gynecologic Malignancies

McMellen¹,

Woodruff²,

Corr

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The blockade of TNKS enzymatic activity results in the accumulation of AXIN1/2-containing β-catenin degradosomes and reduced WNT/β-catenin signaling activity [18,19]. The development of TNKS inhibitors has received focus because of their potential as a possible anticancer treatment strategy, and chemical TNKS inhibition has been shown to impact a number of tumor models [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

Kierulf-Vieira

Sandberg

Waaler

et al. 2020

Cancers

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Evidence suggests that the growth and therapeutic resistance of glioblastoma (GBM) may be enabled by a population of glioma stem cells (GSCs) that are regulated by typical stem cell pathways, including the WNT/β-catenin signaling pathway. We wanted to explore the effect of treating GSCs with a small-molecule inhibitor of tankyrase, G007-LK, which has been shown to be a potent modulator of the WNT/β-catenin and Hippo pathways in colon cancer. Four primary GSC cultures and two primary adult neural stem cell cultures were treated with G007-LK and subsequently evaluated through the measurement of growth characteristics, as well as the expression of WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Treatment with G007-LK decreased in vitro proliferation and sphere formation in all four primary GSC cultures in a dose-dependent manner. G007-LK treatment altered the expression of key downstream WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Finally, cotreatment with the established GBM chemotherapeutic compound temozolomide (TMZ) led to an additive reduction in sphere formation, suggesting that WNT/β-catenin signaling may contribute to TMZ resistance. These observations suggest that tankyrase inhibition may serve as a supplement to current GBM therapy, although more work is needed to determine the exact downstream mechanisms involved.

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Identification of a glycolysis‐related gene signature for survival prediction of ovarian cancer patients

Zhang

Yang

et al. 2021

Cancer Medicine

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Background Ovarian cancer (OV) is deemed the most lethal gynecological cancer in women. The aim of this study was to construct an effective gene prognostic model for predicting overall survival (OS) in patients with OV. Methods The expression profiles of glycolysis‐related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed using training and test sets. Results A gene risk signature based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4) was identified to predict the survival outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high‐grade OV, in the TCGA dataset, with areas under the curve (AUC) of 0.709 and 0.762 for 3‐ and 5‐year survival, respectively. Similar results were found in the test sets, and the AUCs of 3‐, 5‐year OS were 0.714 and 0.772 in the combined test set. And our signature was an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was developed. Conclusion Our study established a nine‐GRG risk model and nomogram to better predict OS in patients with OV. The risk model represents a promising and independent prognostic predictor for patients with OV. Moreover, our study on GRGs could offer guidance for the elucidation of underlying mechanisms in future studies.

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Tankyrase Promotes Aerobic Glycolysis and Proliferation of Ovarian Cancer through Activation of Wnt/β-Catenin Signaling

Cited by 34 publications

References 33 publications

Wnt Signaling in Gynecologic Malignancies

Wnt Signaling in Gynecologic Malignancies

A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

Identification of a glycolysis‐related gene signature for survival prediction of ovarian cancer patients

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