In NAFLD&NASH, we observed that oxidative stress could activate epidermal growth factor receptor (EGFR) to facilitate (i) UBC to repress HSF1 in the WNT and MAPK signaling pathways; (ii) APP to activate ETS1 in the MAPK signaling pathway to induce DNA repair function through the mediation of RFC5, to activate metabolism through the mediation of TRMT1, and to inhibit apoptosis through the mediation of ZNF480; and (iii) SHC1 to repress STAT5A in the MAPK signaling pathway.
Based on two signaling pathways (Figures 5 and 2) involved in core GENs, we found five network biomarkers, UBC, amyloid precursor protein (APP), SHC-transforming protein 1 (SHC1), EGFR, and V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 1 (ETS1), that play a central role in pathogenesis and hepatocarcinogenesis in the upper progression path of Figure 1(a).
Croucher et al., "Temporal regulation of EGF signalling networks by the scaffold protein Shc1," Nature, vol.
p66Shc is a 66 kD Src homologous-collagen homologue (Shc) adaptor protein, which is encoded by the shc1
gene and belongs to the ShcA family.
Of the latter, one gene, SHC1
, appears to interact with 17 other proteins known to have involvement in obesity, and is highly expressed in fat tissue.
The authors suggested that miR365 may induce chemoresistance through directly targeting adaptor protein Src homology 2 domain containing 1 (SHC1) and apoptosis-promoting protein BAX .
Miura et al., 'miR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX," Cell Signal, vol.
GRB2 and SHC1
recruit SOS1 and lead to the activation of Ras-Rafmitogen activated protein kinase (MAPK) pathway that regulates platelet activating factor synthesis, anti-inflammatory responses, and endothelial cell migration, proliferation, permeability, and morphogenesis [5, 20-22, 31, 32].
Among the intracellular components in the insulin-signaling pathway, IGF2 expression was the most abundant, followed by AKT1, IGF2R, INSR, IRS1 and IGF1R, but the mRNA levels of INS1, INS2, PIK3CB, and SHC1 were very low in the adipocytes.
4 and Table 2), and SHC1 mRNA levels that were too low to be compared.
cinnamon extract; DMEM, Dulbecco's modified Eagle's medium; GLUT, glucose transporter; GSK3B, glycogen synthase kinase 3 beta; GYS1, glycogen synthase 1; IGF, insulin-like growth factor; IGFR, insulin-like growth factor receptor; INS, insulin; INSR, insulin receptor; IRS, insulin receptor substrate; LEP, leptin; LEPR, leptin receptor; PIK3CB, phosphatidylinositol 3-kinase, catalytic, beta; PIK3R1, phosphatidylinositol 3-kinase, regulatory subunit 1; RPL32, ribosomal protein L32; SHC1, Src homology 2 domain-containing transforming protein 1; SOS1, Son of sevenless 1; TTP, tristetraprolin; ZFP36, zinc finger protein 36.