2010
DOI: 10.2174/156800910791208535
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Targeting CREB for Cancer Therapy: Friend or Foe

Abstract: The cyclic-AMP response element-binding protein (CREB) is a nuclear transcription factor activated by phosphorylation at Ser133 by multiple serine/threonine (Ser/Thr) kinases. Upon phosphorylation, CREB binds the transcriptional co-activator, CBP (CREB-binding protein), to initiate CREB-dependent gene transcription. CREB is a critical regulator of cell differentiation, proliferation and survival in the nervous system. Recent studies have shown that CREB is involved tumor initiation, progression and metastasis,… Show more

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Cited by 142 publications
(175 citation statements)
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“…In addition to the K-RAS V12 transformants described in this study an upregulated CREB expression and activation was detected in human tumors of distinct origin and appear to contribute to the initiation, progression, and metastatic potential of tumors as well as to a reduced patients' survival (38). In some of these tumor entities, mutations in the ras gene frequently occur, such as colon and lung carcinoma (25,26,39), but a direct link between RAS overexpression and/or mutation and CREB activity has not yet been determined.…”
Section: Discussionmentioning
confidence: 56%
See 1 more Smart Citation
“…In addition to the K-RAS V12 transformants described in this study an upregulated CREB expression and activation was detected in human tumors of distinct origin and appear to contribute to the initiation, progression, and metastatic potential of tumors as well as to a reduced patients' survival (38). In some of these tumor entities, mutations in the ras gene frequently occur, such as colon and lung carcinoma (25,26,39), but a direct link between RAS overexpression and/or mutation and CREB activity has not yet been determined.…”
Section: Discussionmentioning
confidence: 56%
“…This might be mediated by an increased expression of MHC class I surface antigens in shCREB K-RAS V12 transformants (personal communication). Thus, modulation of CREB expression and/or activity might be a potential therapeutic strategy of tumors for growth inhibition (38). This hypothesis is supported by (i) the use of the KIX/KID inhibitor KG-501 leading to a reduced proliferation and migration capacity as well as (ii) by using a dominant negative A-CREB protein inhibiting the DNA binding of the CREB TF family.…”
Section: Discussionmentioning
confidence: 97%
“…The transcription factor CREB1 is crucial for the generation of a malignant autocrine TGFβ2 loop, and hence CREB1 expression/phosphorylation levels might be considered a biomarker of response to anti-TGFβ treatments. Moreover, because CREB1 has been described as a putative therapeutic target ( 36,37 ), our results suggest that compounds against CREB1 could be effective anticancer agents due to their effect on the oncogenic levels of TGFβ2.…”
Section: Research Articlementioning
confidence: 70%
“…Tissue embedding, histology, and immunhistochemistry For the paraffin-embedded human tissues samples, antigen retrieval was performed by microwave treatment for 10 minutes at 750 W in 10 mmol/L of sodium citrate buffer, pH 6.0, and then the 5-mm sections were incubated overnight at 4 C with the pCREB-specific rabbit antibody (clone 87G3; Cell Signaling Technology) at a 1:50 dilution. Antirabbit EnVision kits (K4003, Dako) were used for signal amplification.…”
Section: Patient Selection and Tissue Microarraysmentioning
confidence: 99%
“…1, 2). CREB can be phosphorylated by many different protein kinases, including protein kinase A (PKA), protein kinase B (PKB)/Akt, mitogen-activated protein kinases (MAPK), and p90 ribosomal S6 kinase (p90 metastasis (4,11,12). However, a direct link between oncogenic transformation and CREB has not yet been determined.…”
Section: Introductionmentioning
confidence: 99%