Targeting the overexpressed CREB inhibits esophageal squamous cell carcinoma cell growth

Chen, Ping; Li, Miaomiao; Hao, Qianyun; Zhao, Xuesong; Hu, Tao

doi:10.3892/or.2017.6167

Cited by 11 publications

(12 citation statements)

References 40 publications

(61 reference statements)

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“…In general, whether our data are in contrast to other solid tumors (e.g. esophageal squamous-cell carcinoma, glioma), in which CREB1 expression and activation was associated with higher TNM stage and grading 46,47 , needs to be discussed. However, in Hodgkin lymphoma, CREB1 was found to be tumor suppressive by regulating key aspects of cell proliferation.…”

Section: Discussionmentioning

confidence: 85%

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma

Friedrich

Heimer

Stoehr

et al. 2020

Sci Rep

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The transcription factor cAMP response element-binding protein (CREB1) has been shown to be involved in diverse biological pathways including the regulation of cell proliferation, apoptosis, cell cycle progression, and metastasis. In this context, aberrant expression of CREB1 and the functional consequences are well investigated in a number of hematopoietic and solid tumors. However, CREB1 expression and underlying control mechanisms are only poorly analyzed in renal cell carcinoma (RCC). The present study confirmed a deregulation of CREB1 protein in the clear cell type of RCC (ccRCC) and analysis of in-house ccRCC cell lines suggested a post-transcriptional control. The combination of miRNA enrichment assay, in silico analysis and molecular biological approaches revealed four novel CREB1-regulating miRNAs, namely miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p. Categorizing RCC samples as CREB1 negative or positive, respectively, the expression of these miRNAs was found to be inversely correlated with CREB1 protein levels. Analyzing 453 consecutive RCC tumors by immunohistochemistry, weakly negative, but significant correlations of CREB1 with tumor stage and grade, vascular invasion (V1) and lymphovascular invasion (L1) were found. In this respect, ccRCC might differ from other solid tumors like esophageal squamous-cell carcinoma or glioma.Renal cell carcinoma (RCC) is a kidney cancer originating in the lining of proximal renal tubular epithelial cells and can be histologically subtyped into clear cell type (ccRCC, 75%), papillary (pRCC, 13-15%), chromophobe type (chRCC, 5%), and several rare subtypes 1,2 . Globally, RCC is listed as the sixth most frequently diagnosed form of cancer in men and the tenth in women, with highest rates described in North America and the Czech Republic 3,4 . Noteworthy, RCC incidence was shown to be increasing and frequently accompanied by several risk factors including smoking, hypertension, obesity, chronic analgesic use, and diabetes 5,6 . Early treatment options for RCC are quite limited and usually involve partial or complete resection of the affected kidney(s) 7 since this type of tumor is considerably resistant to chemotherapy and radiotherapy 8 . However, immunotherapy as well as biologic or targeted therapy has shown to be an efficient option for RCC treatment 9 . Thus, it is important to characterize molecular targets responsible for the formation and development of this disease. Probably best analyzed is the alteration of the tumor suppressive Von Hippel-Lindau (VHL) gene that has a crucial value in the origin and development of ccRCC and can be found to be affected in up to 90% of all ccRCC cases 10 . Situated in a complex pathway, VHL is ultimately responsible for the regulation of the transcription factors hypoxia-inducible factor 1 alpha and 2 alpha (HIF1A, HIF2A) 11,12 . The deregulation of HIF1A and HIF2A results in the up-regulation of various growth factors like vascular endothelial growth factor (VEGF), platelet-derived growth factor beta

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Section: Discussionmentioning

confidence: 85%

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma

Friedrich

Heimer

Stoehr

et al. 2020

Sci Rep

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“…Fresh esophageal cancer tissues and adjacent esophageal tissues were collected as previously described . Briefly, fresh esophageal cancer tissues and adjacent esophageal tissues were collected from 24 ESCC patients undergoing resection at the Linzhou Cancer Hospital (Linzhou, Henan, China) from July 2012 to September 2014.…”

Section: Methodsmentioning

confidence: 99%

“…Fresh esophageal cancer tissues and adjacent esophageal tissues were collected as previously described. [35][36][37] For the clonogenic assay, 500 cells were seeded into 6-well plate in triplicate, treated with DMSO or P5091 and then incubated for 12 days. DMSO (0.1%) was used as the vehicle control, and the concentration of P5091 used for Kyse450 cells was 0, 1, 2, 2.5 µmol/L,…”

Section: Collection Of Esophageal Cancer Tissues and Detection Of Tmentioning

confidence: 99%

Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell growth by inducing NOXA‐mediated apoptosis

Zhang

Sha

et al. 2018

Molecular Carcinogenesis

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Increasing evidence suggests that deubiquitinase USP7 participates in tumor progression by various mechanisms and serves as a potential therapeutic target. However, its expression and role in esophageal cancer remains elusive; the anti-cancer effect by targeting USP7 still needs to be investigated. Here, we reported that USP7 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent tissues, implying that USP7 was an attractive anticancer target of ESCC. Pharmaceutical or genetic inactivation of USP7 inhibited esophageal cancer cells growth in vitro and in vivo and induced apoptosis. Mechanistically, inhibition of USP7 accumulated poly-ubiquitinated proteins, activated endoplasmic reticulum stress, and increased expression of ATF4, which transcriptionally upregulated expression of NOXA and induced NOXA-mediated apoptosis. These results provide an evidence for clinical investigation of USP7 inhibitors for the treatment of ESCC.

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“…1). These include acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin's lymphoma, chronic lymphatic leukemia (CLL), melanoma, hepatocellular, renal cell, ovarian, prostate, lung, gastric, esophageal, pancreatic and breast carcinoma, and brain tumors [9][10][11] (Supplementary Table 1).…”

Section: Function Of Creb As a Mediator Of Carcinogenesis: A General mentioning

confidence: 99%

What turns CREB on? And off? And why does it matter?

Steven

Friedrich

Jank

et al. 2020

Cell. Mol. Life Sci.

107

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Altered expression and function of the transcription factor cyclic AMP response-binding protein (CREB) has been identified to play an important role in cancer and is associated with the overall survival and therapy response of tumor patients. This review focuses on the expression and activation of CREB under physiologic conditions and in tumors of distinct origin as well as the underlying mechanisms of CREB regulation by diverse stimuli and inhibitors. In addition, the clinical relevance of CREB is summarized, including its use as a prognostic and/or predictive marker as well as a therapeutic target.

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Targeting the overexpressed CREB inhibits esophageal squamous cell carcinoma cell growth

Cited by 11 publications

References 40 publications

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma

Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell growth by inducing NOXA‐mediated apoptosis

What turns CREB on? And off? And why does it matter?

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