Targeting CREB for cancer therapy: Friend or foe

X. Xiao, B. X. Li, B. Mitton, A. Ikeda, K. M. Sakamoto

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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 transcrip-tional 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, supporting its role as a proto-oncogene. Overexpression and over-activation of CREB were observed in cancer tissues from patients with prostate cancer, breast cancer, non-small-cell lung cancer and acute leukemia while down-regulation of CREB in several distinct cancer cell lines resulted in inhibition of cell proliferation and induction of apoptosis, suggesting that CREB may be a promising target for cancer therapy. Although CREB, as a transcription factor, is a challenging target for small molecules, various small molecules have been discovered to inhibit CREB phosphorylation, CREB-DNA, or CREB-CBP interaction. These results suggest that CREB is a suitable transcription factor for drug targeting and therefore targeting CREB could represent a novel strategy for cancer therapy.

Original languageEnglish (US)
Pages (from-to)384-391
Number of pages8
JournalCurrent Cancer Drug Targets
Volume10
Issue number4
DOIs
StatePublished - 2010

Keywords

  • CBP
  • CREB
  • Cancer
  • Inhibitors
  • KID
  • KIX
  • Naphthol AS-E
  • Ro 31-8220

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

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