Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF-β signalling.
Bottom Line: DACH1 is methylated in 63.3% (62/98) of primary GC and 38% (19/50) of adjacent non-tumour tissues, while no methylation was found in normal gastric mucosa.DACH1 suppresses GC proliferation, invasion and metastasis by inhibiting TGF-β signalling pathways both in vitro and in vivo.Epigenetic silencing DACH1 may induce GC cells' resistance to docetaxel.
Affiliation: Institute of Digestive Diseases, Chinese PLA General Hospital, Beijing, China.Show MeSH
Related in: MedlinePlus
Mentions: DACH1 protein contains two domains: DachBox-N and DachBox-C. Human DachBox-N shares approximately 28% amino acid identity with the SKI/SNO proteins, inhibitors of TGF-β signalling. Thus, the DachBox-N domain is also known as SKI/SNO (DS) domain [25,26]. TGF-β signalling was inhibited by DACH1 in breast and colorectal cancer by DS domain [18,19]. The function of the full-length DACH1, DS (DACH1 fragment, which encodes Smad-binding proteins' domain) and ΔDS (fragment of DACH1 deleted DS) was analysed by Dual-Luciferase reporter assay. SBE4 luciferase activity was inhibited by full-length DACH1 and DS significantly in both BGC823 and AGS cells (P < 0.05, Fig. 3A), but the activity of SBE4 has no changes before and after ΔDS transfection (P > 0.05). The results demonstrate that DS domain is critical for DACH1 function in TGF-β signalling in GC.
Affiliation: Institute of Digestive Diseases, Chinese PLA General Hospital, Beijing, China.