8553

BHLHE40

DEC1 (BHLHE40/Stra13/Sharp2) is a basic helix-loop-helix (bHLH) transcription factor that is involved in the regulation of apoptosis and cell proliferation and the response to hypoxia. epithelial-mesenchymal transition (EMT) is an important step leading to invasion and migration of various tumor cells, and TGF-beta treatment has been shown to induce cancer cells to undergo EMT. However, the significance of DEC1 in TGF-beta-induced EMT remains unknown. We examined the role of DEC1 in EMT of PANC-1 cells, a human pancreatic cancer cell line. As a result, we found that DEC1 was upregulated by TGF-beta in PANC-1 cells, and regulated the expression and the levels of nuclear, cytoplasmic or membrane localization of EMT-related factors, including phosphorylated Smad3 (pSmad3), snail, claudin-4 and N-cadherin. In the presence of TGF-beta, DEC1 knockdown by siRNA inhibited morphological changes during EMT processes, while TGF-beta induced PANC-1 cells to taken on a spindle-shaped morphology. Furthermore, a combination treatment of DEC1 expression with TGF-beta was closely linked to the migration and invasion of PANC-1 cells. Immunohistochemically, DEC1 and pSmad3 were detected within pancreatic cancer tissues, whereas claudin-4 expression was weaker in the cancer tissues compared with the adjacent non-cancer pancreatic tissues. These findings suggest that DEC1 plays an important role in the regulation of these EMT-related factors in pancreatic cancer.

Differentiated embryonic chondrocyte (DEC) 1 has been reported to be involved in cell differentiation, hypoxia response, and cancer progression. Recent studies have demonstrated that hypoxia-inducible factor (HIF)-1alpha induces epithelial-mesenchymal transition (EMT) in carcinoma cells to facilitate cell invasiveness and metastasis. However, it remains unclear whether DEC1 participates in hypoxia-mediated EMT processes. In the present study, we reported that hypoxia induced DEC1 expression in hepatocellular carcinoma (HCC) HepG2 cells, and DEC1 negatively regulated expression of HIF-1alpha and E-cadherin in transcriptional/translational levels. Cell morphological changes were evaluated with hematoxylin and eosin (H-E) staining. Exposure to hypoxia caused spindle-like shape in some of the HepG2 cells, and DEC1 overexpression furthered these changes. In conclusions, DEC1 is involved in hypoxia-induced EMT processes via negatively regulating E-cadherin expression in HepG2 cells.