Tumor-specific inhibitory action of decorin on different hepatoma cell lines

Abstract

Decorin has an inhibitory effect on hepatoma cell lines without respect to their phenotype and molecular background  Decorin is able to block the cell cycle at G2/M phase via phosphorylation of CDK1  In p53 mutant hepatoma cell lines decorin compromises the activity of InsR and IGF-1R  In hepatoma cell lines decorin modulates the activity of main signaling proteins such as AKT, ERK1/2 and β-catenin  Decorin inhibits the production of TGF-β1 by tumor cells 3

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

“…Decorin is also reported to downregulate the phosphorylation of epidermal growth factor receptor, glycogen synthase kinase 3β, and extracellular signal-regulated kinase 1/2 [20]. In addition, decorin suppresses the ATR/Chk1/Wee1 axis, leading to inhibition of the cell cycle in the G2/M phase via phosphorylation of cyclin-dependent kinase 1 [20]. Moreover, decorin is known to decrease the expression of pro-angiogenic factors, vascular endothelial growth factor A, and hypoxia-inducible factor 1-α, resulting in downregulation of the hepatocyte growth factor and epidermal growth factor receptor signaling axes [45].…”

“…Several mechanisms for decorin-induced inhibition of cell proliferation have been reported. Decorin is reported to reduce the secretion of transforming growth factor-β1 in HCC cell lines [20]. Decorin is also reported to downregulate the phosphorylation of epidermal growth factor receptor, glycogen synthase kinase 3β, and extracellular signal-regulated kinase 1/2 [20].…”

“…Decorin is reported to reduce the secretion of transforming growth factor-β1 in HCC cell lines [20]. Decorin is also reported to downregulate the phosphorylation of epidermal growth factor receptor, glycogen synthase kinase 3β, and extracellular signal-regulated kinase 1/2 [20]. In addition, decorin suppresses the ATR/Chk1/Wee1 axis, leading to inhibition of the cell cycle in the G2/M phase via phosphorylation of cyclin-dependent kinase 1 [20].…”

“…We previously reported that serum decorin levels are positively correlated with skeletal muscle mass in patients with HCC [16]. Decorin is also reported to interact with transforming growth factor-β and receptors of tyrosine kinase such as epidermal and insulin-like growth factors [17], leading to suppression of proliferation of various tumor cell lines, including HCC cell lines [18][19][20]. In addition, decorin is known to be expressed in various tissues including intestinal tissue, cardiac tissue, and adipose tissue and is known to regulate autophagy, inflammation, and glucose homeostasis [21][22][23][24].…”

Protective Role of Decorin in Primary Hepatocellular Carcinoma

“…Its action is related to the inhibition of RTKs (20,48,49). Regarding liver tumors, there is hardly any data on the role of decorin in the literature (14,15,42,(50)(51)(52)(53)(54). To fill up this hiatus we hypothesized that decorin may act as a tumor suppressor in HCC.…”