Expression of CPEB, GAPDH and U6snRNA in cervical and ovarian tissue during cancer development

Hansen, Christina; Ketabi, Zohreh; Rosenstierne, Maiken Worsøe; Palle, Connie; Boesen, Hans Christian; Norrild, Bodil

doi:10.1111/j.1600-0463.2008.00015.x

Cited by 67 publications

(59 citation statements)

References 26 publications

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“…For example, like CPEB1 in hippocampal neurons, CPEB4 has been shown to bind and regulate tPA in both normal and cancerous pancreatic tissue (28). Interestingly, several reports implicate a downregulation of CPEB1 in cancer (32)(33)(34), whereas the results presented here suggest that an increase in CPEB1-mediated translation may support the progression of cancer. Because CPEB1 can both inhibit and activate translation, reducing the levels of CPEB1 protein would free mRNA from repression and have the same result as an increase in phosphorylation of CPEB1--namely an increase in target protein expression.…”

Section: Discussioncontrasting

confidence: 55%

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

Kochanek

Wells

2013

Molecular Cancer Research

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Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an mRNA-binding protein present in both neurons and glia. CPEB1 is capable of both repressing mRNA translation and activating it depending upon its phosphorylation state. CPEB1-bound mRNAs are held in translational dormancy until CPEB1 is phosphorylated, leading to the cytoplasmic polyadenylation of the bound mRNA that triggers translation. Here, we show that CPEB1 can bind to and regulate translation of the mRNA-encoding metadherin (MTDH, also known as AEG-1 and Lyric) in the rat glioblastoma cell line CNS1. MTDH/AEG-1 is being revealed as a critical signaling molecule in tumor progression, playing roles in invasion, metastasis, and chemoresistance. By using a mutant of CPEB1 that cannot be phosphorylated (thereby holding target mRNAs in translational arrest), we show that inhibiting CPEB1-mediated translation blocks MTDH/AEG-1 expression in vitro and inhibits glioblastomas tumor growth in vivo. CPEB1-mediated translation is likely to impact several signaling pathways that may promote tumor progression, but we present evidence suggesting a role in directed cell migration in glioblastoma cells. In addition, reporter mRNA containing CPEB1-binding sites is transported to the leading edge of migrating cells and translated, whereas the same mRNA with point mutations in the binding sites is synthesized perinuclearly. Our findings show that CPEB1 is hyperactive in rat glioblastoma cells and is regulating an important cohort of mRNAs whose increased translation is fueling the progression of tumor proliferation and dispersal in the brain. Thus, targeting CPEB1-mediated mRNA translation might be a sound therapeutic approach. Mol Cancer Res; 11(2); 149-60. Ó2012 AACR.

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Section: Discussioncontrasting

confidence: 55%

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

Kochanek

Wells

2013

Molecular Cancer Research

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“…CPEB1 levels are decreased in several types of human tumors, including ovary, stomach and breast cancers, myeloma, as well as colorectal and gastric cancer cell lines and myeloma cell lines (1,20,22,30,31). The reduced levels of CPEB1 have also been associated with the capacity of these malignant cells to promote invasion and angiogenesis (22,32).…”

Section: Cpeb1mentioning

confidence: 99%

“…It has been found to be down-regulated in colorectal cancer through the microarray-based high throughput screening (48). CPEB3 is also down-regulated in human papilloma virus (HPV)-positive cervical cancers compared with normal tissue; this down-regulation of CPEB3 is considered to occur before integration of HPV genome (30). Because CPEB3 is downregulated in colorectal cancer and HPV-positive cervical cancer, it is considered to exert tumor suppression effects.…”

Section: Cpeb3mentioning

confidence: 99%

Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

Chen

Tsai

Tseng

2016

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Abstract. Regulated mRNA translation plays an important role in normal cellular functions and cytoplasmic polyadenylation element binding proteins (CPEBs) are the key factors that control the elongation of poly(A) tail during translation. The expression of various Translation and Cytoplasmic Polyadenylation Element Binding Proteins (CPEBs)Regulated mRNA translation plays an important role in normal cellular functions (1, 2). The translation of an mRNA is divided into three steps: initiation, elongation and termination (1). Among them, translation initiation is the rate-limiting, the most complex and the main target for translational control mechanisms (3). The 5'end of all transcribed mRNAs contains a 5'cap and the other end is blocked by a long stretch, usually in the order of 200-500 nucleotides of adenine residues (poly(A) tail) (1). Both the cap and the poly(A) tail of mRNAs act synergistically to facilitate translation (1). The translation is affected by a number of factors that stimulate or inhibit the translation of specific mRNAs (1, 2). Among these factors, RNAbinding proteins that recognize specific motifs in the 3' untranslated region (3'UTR) of their targets, are important (1, 2, 4). Of these RNA-binding proteins, cytoplasmic polyadenylation element binding protein (CPEB) family are sequence-specific RNA-binding proteins and the key factors controling the elongation of the poly(A) tail and polyadenylation-induced translation (2,5,6). CPEB binds the cytoplasmic polyadenylation element (CPE) in the 3' untranslated regions of responding mRNAs (2, 7-9). CPEB-mediated effects on translation require at least two CPEs separated by less than 50 nucleotides in the target mRNA, which indicates the formation of CPEB-dimer (10). CPEBs can recruit the translational repression or cytoplasmic polyadenylation machineries to their target mRNAs and nucleate a complex of factors that regulates poly(A) elongation through a deadenylating enzyme (1,4,7,(11)(12)(13). 5673

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“…Reducing expression of CAMK2N1 will accelerate tumor growth. 26% of expression variation of CPEB1 that regulates synaptic plasticity and is implied in cancer development (Hansen, et al, 2009) and GRM1 that is involved in neurotransmitter in the central nervous system and implicated in Melanoma (Namkoong, et al, 2007) was explained by overexpressed mir-25 and mir-15b, respectively. Expressions of genes SYT1, SNAP25, GABRA1, VSNL1, MYT1L, SV2B, SYN2 and SLC12A5 which were involved in synaptic transmission, were also largely regulated by miRNAs.…”

Section: Mirna Target Networkmentioning

confidence: 99%