Cross Talk between Wnt/β-Catenin and CIP2A/Plk1 Signaling in Prostate Cancer: Promising Therapeutic Implications

Cristóbal, Ion; Rojo, Federico; Madoz‐Gúrpide, Juan; Garcı́a-Foncillas, Jesús

doi:10.1128/mcb.00130-16

Cited by 20 publications

(16 citation statements)

References 106 publications

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“…and inhibition of PP2A activity . CIP2A controls autophagy and cell growth through mTORC1 activation, synergizes with RAS, and crosstalks with Wnt/β‐catenin signal pathway to promote cell proliferation and cancer progression . It also mediates interleukin 10 (IL‐10)‐induced tumour aggressiveness .…”

Section: Introductionmentioning

confidence: 99%

The red wine component ellagic acid induces autophagy and exhibits anti‐lung cancer activity in vitro and in vivo

Duan

Zhan

Wang

et al. 2018

J Cellular Molecular Medi

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Red wine consists of a large amount of compounds such as resveratrol, which exhibits chemopreventive and therapeutic effects against several types of cancers by targeting cancer driver molecules. In this study, we tested the anti‐lung cancer activity of 11 red wine components and reported that a natural polyphenol compound ellagic acid (EA) inhibited lung cancer cell proliferation at an efficacy approximately equal to that of resveratrol. EA markedly increased the expression of the autophagosomal marker LC3‐II as well as inactivation of the mechanistic target of rapamycin signalling pathway. EA elevated autophagy‐associated cell death by down‐regulating the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), and CIP2A overexpression attenuated EA‐induced autophagy of lung cancer cells. Treating tumour‐bearing mice with EA resulted in significant inhibition of tumour growth with suppression of CIP2A levels and increased autophagy. In addition, EA potentiated the inhibitory effects of the natural compound celastrol on lung cancer cells in vitro and in vivo by enhancing autophagy and down‐regulating CIP2A. These findings indicate that EA may be a promising chemotherapeutic agent for lung cancer, and that the combination of EA and celastrol may have applicability for the treatment of this disease.

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Section: Introductionmentioning

confidence: 99%

The red wine component ellagic acid induces autophagy and exhibits anti‐lung cancer activity in vitro and in vivo

Duan

Zhan

Wang

et al. 2018

J Cellular Molecular Medi

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“…Similarly an alteration of Wnt signalling after the down regulation of PLK1 could also account for observed therapeutic effect in RB cells. An increased PLK1 expression modulated Wnt signalling pathway was identified in prostate cancer 26 .…”

Section: Discussionmentioning

confidence: 99%

EpCAM Aptamer siRNA chimeras: Therapeutic efficacy in epithelial cancer cells

Balasubramanyam

Badrinarayanan

Dhaka

et al. 2019

Preprint

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In the era of personalized medicine as well as precision medicine, targeted therapy has become an integral part of cancer treatment in conjunction with conventional chemo-and radiotherapy. We designed aptamer-siRNA chimeras that can specifically target cancers expressing EpCAM, a stem cell marker and deliver the specific siRNA required for therapy response. The siRNAs were chosen against PLK1, BCL2 and STAT3 as these oncogenes play prominent role in tumour progression of several cancers. Targeted delivery of EpCAM-siRNA chimeras resulted in cell death in several cancer cell lines such as cancers of the breast, lung, head and neck, liver and retinoblastoma. In vivo analysis of EpCAM-siRNA chimera mediated silencing on RB xenografts tumour model showed increased tumor reduction in all the three EpCAM-siRNA treated conditions. However, regulation of PLK1 exhibited higher efficacy in tumour reduction. Therefore. We studied signaling mechanism using global phosphoproteomics analysis. An increased P53 mediated downstream signalling pathway might have enabled increased apoptosis in the cancer cells. In conclusion, this study demonstrated the efficacy of EpCAM aptamer chimeras coupled to siRNA gene silencing for targeted anti-cancer therapy.

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“…Due to the involvement of Wnt/β‐catenin pathway in progression, it has been suggested to act as a molecular marker for predicting resistance to several androgen‐dependent therapies . Due to their important role in tumorigenesis and metastasis, genes involved in canonical and non‐canonical Wnt signaling pathways are emerging as promising targets for therapeutic intervention in PCa . Future studies are needed to not only understand the mechanism of Wnt signaling driven PCa but also identify race‐specific therapeutic potential.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic analysis identifies factors driving racial disparity in prostate cancer

et al. 2018

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Background Prostate cancer (PCa) is the second most leading cause of death in men worldwide. African‐American men (AA) represent more aggressive form of the disease compared to Caucasian (CA) counterparts. Several lines of evidences suggest that biological factors are responsible for the observed racial disparity. Aim This study was aimed at identifying the epigenetic variation among AA and CA PCa patients and whether DNA methylation differences have an association with clinical outcomes in the two races. Methods and results The cancer genome atlas (TCGA) dataset (2015) was used to identify existing epigenetic variation in AA and CA PCa patients. Reduced Representation Bisulfite Sequencing (RRBS) was performed to identify global DNA methylation changes in a small cohort of AA and CA PCa patients. The RRBS data were then used to identify survival and recurrence outcomes in AA and CA PCa patients using publicly available datasets. The TCGA data analysis revealed epigenetic heterogeneity, which could be categorized into four classes. AA associated primarily to methylation cluster 1 (p = 0.048), and CA associated to methylation cluster 3 (p = 0.000146). Enrichment of the Wnt signaling pathway was identified in both the races; however, they were differentially activated in terms of canonical and non‐canonical Wnt signaling. This was further validated using the Decipher Genomics Resource Information Database (GRID). The RRBS data also identified discrete methylation patterns in AA compared with CA and, in part, validated our TCGA findings. Survival analysis using the RRBS data suggested hypomethylated genes to be significantly associated with recurrence of PCa in CA (p = 6.07 × 10−6) as well as in AA (p = 0.0077). Conclusion Overall, we observed epigenetic‐based racial disparity in PCa which could affect survival and should be considered during prognosis and treatment.

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Cross Talk between Wnt/β-Catenin and CIP2A/Plk1 Signaling in Prostate Cancer: Promising Therapeutic Implications

Cited by 20 publications

References 106 publications

The red wine component ellagic acid induces autophagy and exhibits anti‐lung cancer activity in vitro and in vivo

The red wine component ellagic acid induces autophagy and exhibits anti‐lung cancer activity in vitro and in vivo

EpCAM Aptamer siRNA chimeras: Therapeutic efficacy in epithelial cancer cells

Epigenetic analysis identifies factors driving racial disparity in prostate cancer

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