<b>Decrease of phosphorylated proto-oncogene<i>CREB</i>at Ser 133 site inhibits growth and metastatic activity of renal cell cancer</b>

Wang, Xue; Ren, Yu; Zhuang, Haihui; Meng, Xiangyu; Huang, Shuaishuai; Li, Yanyuan; Hehir, M.; Wang, Ping

doi:10.1517/14728222.2015.1053208

Cited by 24 publications

(29 citation statements)

References 52 publications

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“…Previous reports showed that CREB promoted cancer metastasis (12,14,43,44). CREB regulated vascular endothelial growth factor expression and was involved in human prostate cancer bone metastasis (45).…”

Section: Discussionmentioning

confidence: 95%

Targeting the overexpressed CREB inhibits esophageal squamous cell carcinoma cell growth

Chen

Hao

et al. 2017

Oncol Rep

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Abstract. Although several studies highlight the important role of cAMP-responsive element binding protein (CREB) in tumor progression, little is known concerning the expression and function of CREB in esophageal cancer. In the present study, the expression of CREB was evaluated using a human esophageal squamous cell carcinoma tissue array by immunohistochemical analysis, which was confirmed by western blot analysis of tissues from esophageal cancer, and adjacent esophageal tissue. The role of CREB on esophageal cancer cell growth was analyzed in vitro and in vivo. Results showed that CREB was overexpressed in esophageal squamous cell carcinomas tissues, which was positively correlated with lymph node metastasis and tumor-node-metastasis (TNM) stage of esophageal cancer patients. Downregulating the expression of CREB effectively reduced esophageal cell growth in vitro and in vivo, induced S phase cell cycle arrest, triggered apoptosis and inhibited cell migration and invasion. These findings suggested CREB as an attractive drug target for esophageal cancer.

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Section: Discussionmentioning

confidence: 95%

Targeting the overexpressed CREB inhibits esophageal squamous cell carcinoma cell growth

Chen

Hao

et al. 2017

Oncol Rep

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“…CREB, a common downstream target of AKT, is a proto-oncogenic transcription factor, which generally regulates various cell functions by enhancing the expression of target genes [32,33]. Our previous studies indicated that the over-expression and abnormal activation of CREB celebrate tumorigenesis and tumor migration [34,35]. Therefore, we postulated that overexpression of PNN promotes prostate cancer progression through activating PI3K/AKT/CREB signaling axis.…”

Section: Pnn Regulates Prostate Cancer Cell Proliferation and Migratimentioning

confidence: 96%

Pinin promotes tumor progression via PI3K/AKT/CREB signaling pathway in prostate cancer

Meng

Zhang²,

Ren

et al. 2020

Preprint

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Abstract Background Pinin (PNN), a desmosome associated protein, was demonstrated to be over-expressed and act as a tumor-promoting factor in ovarian cancer, hepatocellular carcinoma and colorectal cancer. However, the precise role of PNN in prostate cancer is still unknown. Methods The expression levels of PNN were assessed in prostate cancer by qRT-PCR, western blotting and immunohistochemical staining. The other proteins were quantified by western blotting. PNN-depleted cells were produced by infecting with lentivirus bearing short hairpin RNAs against PNN. PNN over-expression was performed by transfecting PNN expression vector. The proliferation of each cell line was assessed by MTS and colony formation assays. Tumors were induced on nude mice by injecting tumor cells subcutaneously. Apoptosis and cell cycle were evaluated by flow cytometry. Transwell and wound healing assay were performed to determined the ability of cell invasion and migration. The TCGA data were analyzed with GEPIA (Gene Expression Profiling Interactive Analysis) and GraphPad Prism. Results Here, we reported that PNN was upregulated in prostate cancer tissues and PNN expression was positively associated with Gleason score, tumor stage and tumor metastasis. PNN promoted cell growth and tumorigenicity in vitro and in vivo, and might modulate cell growth through driving G1/S transition via CDK6, CDK2, and Cyclin D1 in prostate cancer cells. Furthermore, PNN accelerated cell invasion, migration and EMT processes of prostate cancer cells accompanied with the up-regulation of MMP-2, MMP-9, N-cadherin, Vimentin and down-regulation of E-cadherin. Mechanism study demonstrated that the proliferation- and motility-promoting effects of PNN on prostate cancer cells dependent on the activation of PI3K/AKT/CREB signaling, which was reversed by AKT and CREB inhibitors. Conclusions Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it may be a potential therapeutic target for prostate cancer treatment.

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“…Our previous study demonstrated that pCREB was upregulated in human renal cancer cell lines and tissues. Lentiviral vector production was used to knockdown the expression of pCREB in OS-RC-2 cells and the results demonstrated that decreasing the level of pCREB inhibited the growth and metastasis of OS-RC-2 cells (21). However, although the results are promising, further studies are needed to confirm this.…”

Section: Cyclic Amp Responsive Element-binding Protein Induces Metastmentioning

confidence: 99%

Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition

Wang¹,

Cui²,

Lou³

et al. 2017

Molecular Medicine Reports

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Renal cell carcinoma (RCC) is the most frequently occurring malignancy of the kidney worldwide. Anti-angiogenic targeted therapies inhibit the progression of RCC, however, limited effects on the invasion or metastasis of tumor cells have been observed. Cyclic AMP responsive element‑binding protein (CREB) is a serine/threonine kinase that has been implicated in the regulation of cell proliferation, apoptosis, cycle progression and metastasis, amongst others. Our previous research demonstrated that phosphorylated CREB (pCREB) was upregulated in human renal cancer cell lines and tissues, and decreased pCREB at the Ser133 site inhibited the growth and metastatic activity of OS‑RC‑2 cells. However, the role of CREB in RCC metastasis requires further investigation. Thus, the present study further investigated the role of CREB in RCC metastasis. The present study demonstrated that knockdown of CREB using small interfering RNA (siRNA) that targeted CREB (siCREB) significantly inhibited the migration and invasion of 786‑O and OS‑RC‑2 cells, however, the opposite effect was observed in ACHN cells. In addition, knockdown of CREB suppressed the expression of matrix metallopeptidase (MMP)‑2/9 and proteins associated with epithelial‑mesenchymal transition (EMT) in 786‑O and OS‑RC‑2 cells, and promoted expression in ACHN cells. Furthermore, the chromatin immunoprecipitation assay indicated that pCREB (Ser133) had a direct interaction with the fibronectin promoter, however, pCREB (Ser133) did not target the vimentin promoter in RCC. Therefore, the results of the present study indicate that CREB regulated metastatic RCC by mediating the expression of MMP‑2/9 and EMT‑associated proteins, however, CREB‑mediated MMP‑2/9 and EMT‑associated protein expression may be induced by different pathways in different RCC cells.

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Decrease of phosphorylated proto-oncogeneCREBat Ser 133 site inhibits growth and metastatic activity of renal cell cancer

Abstract: These data suggest that decreasing the level of pCREB inhibits the growth and metastasis of RCC by targeting the Ser 133 site.

Cited by 24 publications

References 52 publications

Targeting the overexpressed CREB inhibits esophageal squamous cell carcinoma cell growth

Targeting the overexpressed CREB inhibits esophageal squamous cell carcinoma cell growth

Pinin promotes tumor progression via PI3K/AKT/CREB signaling pathway in prostate cancer

Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition

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