β-arrestin1 promotes epithelial-mesenchymal transition via modulating GSK-3β/β-catenin pathway in prostate cancer cells

Duan, Xiaolu; Zhang, Tao; Kong, Zhenzhen; Mai, Xin; Lan, Chuangxin; Chen, Dong; Liu, Yang; Zeng, Zhiwen; Cai, Chao; Deng, Tuo; Wu, Wenqi; Zeng, Guohua

doi:10.1016/j.bbrc.2016.09.039

Cited by 22 publications

(31 citation statements)

References 39 publications

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“…E, Western blot analysis of the effects of LY294002 on the E-cadherin, slug, Akt, p-Akt-S473, GSK-3b, p-GSK-3b protein levels in EYA4-knockdown cells and control cells GSK-3b signaling pathway is involved in the progression of EMT in human malignancies, such as gastric cancer, hepatocellular carcinoma and prostate cancer. [29][30][31] In this study, we found that in EYA4-knockdown cells, the expression of p-AKT, p-GSK-3b and slug were significantly increased. Moreover, an immunofluorescence assay detected the localization of slug in the EYA4-knockdown cells and F I G U R E 7 EYA4 plays a role in DNA damage repair in esophageal squamous cell carcinoma (ESCC).…”

Section: Discussionmentioning

confidence: 51%

“…EMT is a critical event in the progression toward cancer metastasis and many signaling pathways are involved in the regulation of EMT in ESCC, such as Akt/GSK‐3β/Snail, MAPK/ERK and TGF‐β1/Smad . Several studies have reported that the AKT/GSK‐3β signaling pathway is involved in the progression of EMT in human malignancies, such as gastric cancer, hepatocellular carcinoma and prostate cancer . In this study, we found that in EYA4‐knockdown cells, the expression of p‐AKT, p‐GSK‐3β and slug were significantly increased.…”

Section: Discussionmentioning

confidence: 52%

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Aberrant methylation of EYA4 promotes epithelial‐mesenchymal transition in esophageal squamous cell carcinoma

Luo

Shi

et al. 2018

Cancer Science

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EYA4, one of the four members of the EYA gene family, is associated with several human cancers. However, its biological functions and molecular mechanisms in the progression of cancer, particularly in esophageal squamous cell carcinoma (ESCC), remain unknown. In the present study, we found that EYA4 was underexpressed and hypermethylated in most of the ESCC cell lines tested (85.7%, 6/7). Treatment with 5‐aza‐dC and/or trichostatin A (TSA) restored EYA4 expression in ESCC cell lines, which indicates that EYA4 expression was epigenetically regulated. Similarly, EYA4 was aberrantly hypermethylated in ESCC tissues (78%, 39/50) and downregulation of EYA4 occurred in approximately 65% of primary ESCC at protein level where it was associated significantly with TNM stage and lymph node metastases. Knockdown of EYA4 in KYSE30 and KYSE70 ESCC cells using small hairpin RNA increased migration and invasive motility in vitro. Conversely, the overexpression of EYA4 in KYSE180 and KYSE450 promoted an epithelial phenotype, which consisted of decreased migration and invasion abilities and a decrease in TGF‐β1‐induced epithelial‐mesenchymal transition. Mechanistically, EYA4 overexpression reduced the phosphorylation of Akt and glycogen synthase kinase (GSK) 3β, which led to the inactivation of slug. In addition, we found that TGF‐β1 decreased EYA4 expression in both a dose‐dependent and a time‐dependent manner in KYSE30 cells, accompanied by an increase in the expression of DNA methyltransferases, especially DNMT3A. In summary, EYA4 is frequently hypermethylated in ESCC and may function as a tumor suppressor gene in the development of ESCC.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 52%

Aberrant methylation of EYA4 promotes epithelial‐mesenchymal transition in esophageal squamous cell carcinoma

Luo

Shi

et al. 2018

Cancer Science

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“…Previous studies have indicated that β‐arrestins play an impressive role in tumor progression through regulating signal transductions which are responsible for tumor viability and metastasis . Although the role of β‐arrestin1 in cell survival and proliferation has been well established in ovarian, gastric, lung and breast cancers, and more recently, β‐arrestin1 was identified to act as a potential tumor promoter in PCa, its underlying mechanism has still not been well clarified …”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence reveals that β‐arrestin1 can also serve as an adaptor to guide signals from distinct pathways that play important roles in cell proliferation, apoptosis and cancer progression through interacting with different signaling molecules . Recently, β‐arrestin1 has been identified as a potential tumor promoter by promoting cell proliferation and epithelial to mesenchymal transition in PCa, but its underlying mechanism is still not well clarified…”

Section: Introductionmentioning

confidence: 99%

β‐arrestin1‐medieated inhibition of FOXO3a contributes to prostate cancer cell growth in vitro and in vivo

et al. 2018

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Recently, β‐arrestin1 has been indicated as a prostate cancer promoter through promoting cell proliferation and epithelial to mesenchymal transition, but its underlying mechanism remains unclear. Here, our data revealed that β‐arrestin1 could promote cell growth through inhibiting the transcriptional activity and expression of FOXO3a in prostate cancer cells in vitro and in vivo. We found that β‐arrestin1 could promote the cell and tumor growth of prostate cancer, and β‐arrestin1 expression represented a negative correlation with FOXO3a expression but not FOXO1 expression in prostate cancer cell lines and tissues. In addition, forced expression of β‐arrestin1 induced a significant decrease of FOXO3a expression but had no clear effect on FOXO1 expression. Mechanistically, β‐arrestin1 could interact with FOXO3a and MDM2, respectively, and promote the interaction between FOXO3a and MDM2, whereas it had no obvious interaction with FOXO1. Furthermore, β‐arrestin1 could inhibit the transcriptional activity of FOXO3a via Akt and ERK1/2 pathways. Together, our results revealed a novel mechanism for β‐arrestin1 in the regulation of the prostate cancer procession through inhibiting FOXO3a.

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“…β ‐Arrestin1 just acts as the ultimate effect element during CD97 internalization process. Recently, the promoting role of β ‐arrestin1 in ovarian cancer, lung cancer, prostate cancer, and breast cancer metastasis has been raised . The role of β ‐arrestin1 in our study can be interpreted in the context of the canonical GPCR trafficking element during CD97 internalization.…”

Section: Discussionmentioning

confidence: 56%

CD97 Promotes Tumor Aggressiveness Through the Traditional G Protein–Coupled Receptor–Mediated Signaling in Hepatocellular Carcinoma

Yin

Tang

et al. 2018

Hepatology

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Cluster of differentiation 97 (CD97) is a member of the epidermal growth factor seven-transmembrane family belonging to the class B G protein-coupled receptors (GPCRs). The protein affects tumor aggressiveness through its cellular ligand CD55 stimulation and exhibits adhesive properties. Studies have demonstrated the involvement of CD97 in dedifferentiation, migration, invasiveness, and metastasis of tumors. However, little information is currently available on the specific role of CD97 in hepatocellular carcinoma (HCC). Here, we have shown that CD97 up-regulation in HCCs is positively correlated with tumor metastasis. Functionally, CD97 promoted cell migration and invasion in vitro. In an in vivo mouse model, overexpression of CD97 in HCC cells led to accelerated lung metastasis. Mechanistically, CD97 cooperated with the altered regulator, GPCR kinase 6 (GRK6), to mediate GPCR desensitization and internalization. Down-regulation of GRK6 suppressed CD97 internalization and promoted CD97 expression. Integrated regulatory interactions between CD97 and GRK6 stimulated downstream matrix metalloproteinase 2/9 secretion and, consequently, HCC metastasis. Conclusion: Our collective findings support the utility of CD97 as an effective potential prognosticator and therapeutic target for HCC.

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β-arrestin1 promotes epithelial-mesenchymal transition via modulating GSK-3β/β-catenin pathway in prostate cancer cells

Cited by 22 publications

References 39 publications

Aberrant methylation of EYA4 promotes epithelial‐mesenchymal transition in esophageal squamous cell carcinoma

Aberrant methylation of EYA4 promotes epithelial‐mesenchymal transition in esophageal squamous cell carcinoma

β‐arrestin1‐medieated inhibition of FOXO3a contributes to prostate cancer cell growth in vitro and in vivo

CD97 Promotes Tumor Aggressiveness Through the Traditional G Protein–Coupled Receptor–Mediated Signaling in Hepatocellular Carcinoma

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