Poly(A)-binding Protein-interacting Protein 2, a Strong Regulator of Vascular Endothelial Growth Factor mRNA

Onesto, Cercina; Berra, Edurne; Grépin, Renaud; Pagès, Gilles

doi:10.1074/jbc.m400219200

Cited by 71 publications

(52 citation statements)

References 39 publications

(50 reference statements)

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“…Adenylate-and uridylaterich elements present in the 3Ј-UTR of many short lived mRNAs, such as those of growth factors, cytokines, proto-oncogenes, and cell cycle regulatory genes, have been linked to the stability of these mRNAs, and a variety of RNA-binding proteins that selectively bind to adenylate-and uridylate-rich elements of these mRNAs have been identified (34). Although several RNA-binding proteins, such as HuR (20), heterogeneous nucleo ribonucleoprotein L (21), and poly(A)-binding protein-interacting protein 2 (35), have been demonstrated to bind to the 3Ј-UTR of VEGF mRNA and to participate in mRNA stabilization under hypoxic conditions, it is unknown whether or not hypoglycemia-induced VEGF mRNA stability is mediated by the similar proteins and mechanisms. We are currently investigating such a possibility and attempting to identify a component(s) involved in VEGF mRNA stabilization, which is directly regulated by AMPK.…”

Section: Jnk Acts As An Upstream Component In Ampk Activationmentioning

confidence: 99%

Glucose Deprivation Increases mRNA Stability of Vascular Endothelial Growth Factor through Activation of AMP-activated Protein Kinase in DU145 Prostate Carcinoma

Lee

Kim

et al. 2005

Journal of Biological Chemistry

137

102

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The induction of proangiogenic cytokines such as vascular endothelial growth factor (VEGF) is a critical feature of tumor angiogenesis. In the present study, we examined the mechanisms of VEGF gene expression induced by glucose deprivation in cancer cells, a role of AMP-activated protein kinase (AMPK) in the process, and the signal transduction pathway. AMPK functions as an energy sensor to provide metabolic adaptation under ATP-depleting conditions such as hypoxia and nutritional deprivation. Here, we show that glucose deprivation leads to a significant increase in the mRNA level of VEGF, GLUT1, and PFKFB3 genes in several cancer cells via a hypoxia-inducible factor-1-independent mechanism, and we demonstrate an essential role of AMPK in these gene expressions. Our data suggest that VEGF mRNA induction by glucose deprivation is due to an increase in mRNA stability, and the AMPK activity is necessary and sufficient to confer the stability to VEGF mRNA. We further show that reactive oxygen species is involved in glucose deprivation-induced AMPK activity in DU145 human prostate carcinomas, and c-Jun aminoterminal kinase acts as an upstream component in AMPK activation cascades under these conditions. LKB1, which was recently identified as a direct upstream kinase of AMPK, was not detected in DU145 cells. In conclusion, our results demonstrate a novel and major role of AMPK in the post-transcriptional regulation of VEGF, further implying its potential role in tumor angiogenesis.

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Section: Jnk Acts As An Upstream Component In Ampk Activationmentioning

confidence: 99%

Glucose Deprivation Increases mRNA Stability of Vascular Endothelial Growth Factor through Activation of AMP-activated Protein Kinase in DU145 Prostate Carcinoma

Lee

Kim

et al. 2005

Journal of Biological Chemistry

137

102

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“…VEGF is tightly regulated at the transcript level, and although its reported half-life is short (15-40 min in vitro),this can be substantially extended during periods of hypoxia and nutrient withdrawal (Ikeda et al 1995, Shima et al 1995, Levy et al 1996, Dibbens et al 1999). AU-rich elements within the 3 0 UTR of the VEGF transcript, along with other elements within the coding and UTRs, are potential targets for a range of RNA-binding proteins that have been shown to result in both positive and negative effects on transcript stability (Claffey et al 1998, Shih & Claffey 1999, King 2000, Goldberg-Cohen et al 2002, Coles et al 2004, Onesto et al 2004, Fellows et al 2012, Chang et al 2013. Hypoxia-dependent regulation of transcript stability has been well characterized in a number of cancer types and was recently reviewed by Arcondeguy et al (2013).…”

Section: Post-transcriptional Regulation Of Vegf Signaling In Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

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“…Moreover, we have recently demonstrated in several tumour cell lines that VEGF-A expression is highly regulated by an RNAbinding and stabilizing partner of the VEGF-A mRNA, the Poly(A) binding protein-interacting protein 2 (PAIP2) (Onesto et al, 2004). Thus, we investigated in the present study whether VEGF-A expression is associated with PAIP2 expression in HNSCC and examined whether PAIP2 expression is related to clinicopathological parameters and patient's survival.…”

mentioning

confidence: 99%

Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance

Onesto

Chamorey

et al. 2006

Br J Cancer

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Vascular endothelial growth factor-A (VEGF-A) has been demonstrated to play an important role in tumour angiogenesis and to influence prognosis in many cancers. However its prognostic value in head and neck squamous cell carcinomas (HNSCCs) remains controversial. Therefore, we investigated the clinical relevance of VEGF-A expression in HNSCCs and analysed whether its expression was associated with PAIP2 protein levels, a VEGF-A mRNA-binding partner that strongly regulates VEGF-A expression in tissue culture. We determined the correlation of VEGF-A and PAIP2 protein levels, quantitatively evaluated in tumour tissue homogenates from 54 patients with HNSCC, to clinicopathological parameters. We showed that VEGF-A expression in HNSCC is correlated to the stage of tumour differentiation ( P =0.050) and is an independent prognostic factor for progression-free survival ( P =0.001) and overall survival ( P =0.0004). In a pharynx carcinoma cell line, we demonstrated by RNA interference that VEGF-A expression is closely controlled by PAIP2. Moreover, in human HNSCCs, VEGF-A expression is significantly correlated to PAIP2 protein levels ( P =0.0018). Nevertheless, PAIP2 expression is associated with neither clinicopathological factors nor patient's survival. Our data suggest that, in contrast to PAIP2 protein levels, which are unrelated to tumour prognosis, VEGF-A expression could serve as a prognostic marker in head and neck cancer and may be helpful for targeted therapies.

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Poly(A)-binding Protein-interacting Protein 2, a Strong Regulator of Vascular Endothelial Growth Factor mRNA

Cited by 71 publications

References 39 publications

Glucose Deprivation Increases mRNA Stability of Vascular Endothelial Growth Factor through Activation of AMP-activated Protein Kinase in DU145 Prostate Carcinoma

Glucose Deprivation Increases mRNA Stability of Vascular Endothelial Growth Factor through Activation of AMP-activated Protein Kinase in DU145 Prostate Carcinoma

Regulation of vascular endothelial growth factor in prostate cancer

Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance

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