Regulatory mechanisms of the HB-EGF autocrine loop in inflammation, homeostasis, development and cancer.
Heparin binding epidermal growth factor-like growth factor (HB-EGF) is involved in development and homeostasis as well as in pathological processing of chronic diseases, especially cancer. Enhancement of HB-EGF expression is directly or indirectly regulated by transcriptional factors, including activator protein-1 (AP-1), specificity protein (SP)1, SP3, nuclear factor kappa B (NF-κB), hypoxia inducible factor 1, alpha subunit (HIF-1α, myogenic differentiation 1 (MyoD), Wilms tumor 1 (WT-1) and snail homolog 1 (Snail), and also by microRNAs. These transcription or post-transcription factors may communicate to form an autocrine HB-EGF amplification loop. Emerging evidence has indicated that HB-EGF is a rational target for the therapy of cancer and atherosclerosis. In this review, we discuss the relationship between the HB-EGF autocrine loop and HB-EGF transcriptional factors, and we highlight HB-EGF as a therapeutic target in diverse diseases.
Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Kohei
K
Miyata
Fusanori
F
Yotsumoto
Sung Ouk
SO
Nam
Masahide
M
Kuroki
Shingo
S
Miyamoto
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins