Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP

Seo, Won Ik; Park, Seoyoung; Gwak, Jungsug; Ju, Bong Gun; Chung, Jae Il; Kang, Pil Moon; Oh, Sangtaek

doi:10.1016/j.bbrc.2017.03.158

Cited by 26 publications

(30 citation statements)

References 21 publications

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“…26 Altered expression of YAP could be a result of deregulation at multiple levels. 28 MiR-302/367 cluster could decrease LATS2 level to stabilize YAP protein and thus accelerating PCa cell growth. A-C, Transfection of miR-10a mimics decreased YAP mRNA and protein levels in both LNCaP cells and PC-3 cells.…”

Section: Discussionmentioning

confidence: 99%

MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A

Xiang

et al. 2018

J of Cellular Biochemistry

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Deregulation of microRNAs contributes to the abnormal cell growth which is frequently observed in cancer. In the current study, we detected the expression and regulatory relationship between miR‐10a and Lysine‐specific demethylase 4A (KDM4A) to reveal their function in prostate cancer (PCa) progression. We found that miR‐10a levels were significantly decreased in PCa cell lines in comparison with the normal epithelial cell line RWPE‐1. Downregulation of miR‐10a levels was also observed in tumor tissues from PCa patients compared with the adjacent normal tissues. Enhanced expression of miR‐10a inhibited cell proliferation and colony forming capability of PCa cells. In addition, quantitative real‐time polymerase chain reaction and Western blot analysis showed a significant decrease of KDM4A in response to miR‐10a elevation in PCa cells. Using dual luciferase assay, we confirmed that KDM4A was a target gene for miR‐10a. Furthermore, Western blot analysis indicated that miR‐10a overexpression inactivated YAP signaling and suppressed transcription of YAP target genes. Additionally, cell growth arrest and colony forming capacity inhibition induced by miR‐10a overexpression could be reversed by YAP overexpression in PCa cells. More importantly, miR‐10a mimics inhibited PC‐3 tumor growth in nude mice accompanied with a remarkable reduction of KDM4A and YAP expression. In conclusion, our results uncovered a tumor suppressor role of miR‐10a in PCa via negative regulation of KDM4A and its downstream Hippo‐YAP pathway.

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Section: Discussionmentioning

confidence: 99%

MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A

Xiang

et al. 2018

J of Cellular Biochemistry

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“…Wnt pathway is well‐known for contributing to tumor malignancy in multiple cancers, which also serves as the pivotal mechanism driving tumor progression in GIST, announced by several previous evidences . As a canonical Wnt pathway antagonist, DKK4 belonging to dickkopf (DKK) families is also transcriptionally activated by Wnt pathway transcriptional factor, forming an ideal regulatory loop .…”

Section: Introductionmentioning

confidence: 99%

Aberrant accumulation of Dickkopf 4 promotes tumor progression via forming the immune suppressive microenvironment in gastrointestinal stromal tumor

Wang

Zhuang

et al. 2019

Cancer Medicine

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Background Drug resistance and tumor recurrence are the major concerns in clinical practices of gastrointestinal stromal tumor (GIST), with the urgent requirement for exploring undiscovered pathways driving malignancy. To deal with these, recent studies have made many efforts to explore prognosis indicators and establish potential therapeutic targets. Methods Expression profiles of different risks of GISTs were described and abundant clinical evidences supported our findings in this study. Following exploration in vitro by cell experiments and verification in vivo using tumor microarray were taken to elucidate the underlying mechanism, which drove the malignancy in GIST. Results Dickkopf 4 (DKK4), as the canonical Wnt pathway antagonist, was unexpectedly and universally upregulated in high‐risk GISTs, and aberrant accumulation of DKK4 was closely correlated with poor prognosis. In addition, tumor‐derived DKK4 could decrease immune cells infiltration and activation in the tumor microenvironment, which decreased the antitumor effects in return. And this phenomenon was recurrent in human tumor specimens. Conclusions Our findings identified DKK4 as a proper tumor biomarker for prognosis predicting and recurrence monitoring, and suggested a novel immune‐escape mechanism driving malignancy in GIST, which might be a potential therapeutic target to improve the effects of canonical RTK therapy and combined immunotherapy.

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“…Recent studies have demonstrated that the Hippo/YAP pathway can crosstalk with other signalling pathways to regulate a series of biological functions in cancer, which is greatly depends on the important role of YAP that is not only mediated by the upstream signal molecule, but can also regulate a series of targets via interacting with transcription factors. By analysing studies published in recent years, we can summarize a complex regulatory network in which YAP is involved in a series of signalling pathways (Figure 1 ), such as those involving TGF-β/SMAD [ 67 , 68 ], Wnt/β-catenin [ 69 , 70 ], epidermal growth factor receptor (EGFR) [ 39 , 71 ], PI3K-AKT [ 72 , 73 ], NF-κB [ 69 , 74 ], Sonic Hedgehog (Shh) [ 75 , 76 ], mTOR [ 77 , 78 ], IL6 receptor (IL-6R) [ 79 , 80 ], GPCR [ 81 , 82 ], and Notch [ 83 , 84 ].…”

Section: Introductionmentioning

confidence: 99%

Dual roles of yes-associated protein (YAP) in colorectal cancer

Sun

Shen

et al. 2017

Oncotarget

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Yes-associated protein (YAP) is a downstream effector molecule of a newly emerging tumour suppressor pathway called the Hippo pathway. YAP is a transcriptional co-activator and mis-expressed in various cancers, including colorectal cancer (CRC). Accumulating studies show that the high expression of nuclear YAP is linked with tumour progression and decreased survival. Nuclear YAP can interact with other transcription factors to promote cancer cell proliferation, apoptosis, metastasis and maintenance of stemness. Therefore, YAP has the potential to be a tumour biomarker or therapeutic target for CRC. However, recently, a number of studies have supported a contradictory role for YAP as a tumour suppressor, demonstrating inhibition of the tumorigenesis of CRC, involvement in promoting cell apoptosis, and inhibiting the maintenance of intestinal stem cells and inflammatory activity. In these studies, high expression of YAP was highly correlated with worse survival in CRC. In this review, we will comprehensively summarize and analyse these paradoxical reports, and discuss both the oncogenic and tumour suppressor functions of YAP in the differential status of CRC progression. Further investigation into the mechanisms responsible for the dual function of YAP will be of great value in the prevention, early diagnosis, and therapy of CRC.

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Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP

Cited by 26 publications

References 21 publications

MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A

MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A

Aberrant accumulation of Dickkopf 4 promotes tumor progression via forming the immune suppressive microenvironment in gastrointestinal stromal tumor

Dual roles of yes-associated protein (YAP) in colorectal cancer

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