DKK3 blocked translocation of β‐catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc‐3 cell

Abstract

The Wnt/β‐catenin signalling pathway is activated in pancreatic cancer initiation and progression. Dickkopf‐related protein 3 (DKK3) is a member of the human Dickkopf family and an antagonist of Wnt ligand activity. However, the function of DKK3 in this pathway in pancreatic cancer is rarely known. We examined the expression of DKK3 in six human pancreatic cancer cell lines, 75 pancreatic cancer and 75 adjacent non‐cancerous tissues. Dickkopf‐related protein 3 was frequently silenced and methylation in pancreatic cancer cell lines (3/6). The expression of DKK3 was significantly lower in pancreatic cancer tissues than in adjacent normal pancreas tissues. Further, ectopic expression of DKK3 inhibits nuclear translocation of β‐catenin induced by hypoxia in pancreatic cancer Bxpc‐3 cell. The forced expression of DKK3 markedly suppressed migration and the stem cell‐like phenotype of pancreatic cancer Bxpc‐3 cell in hypoxic conditions through reversing epithelial–mesenchymal transition (EMT). The stable expression of DKK3 sensitizes pancreatic cancer Bxpc‐3 cell to gemcitabine, delays tumour growth and augments gemcitabine therapeutic effect in pancreatic cancer xenotransplantation model. Thus, we conclude from our finding that DKK3 is a tumour suppressor and improved gemcitabine therapeutic effect through inducing apoptosis and regulating β‐catenin/EMT signalling in pancreatic cancer Bxpc‐3 cell.

Decreased expression of acetyl‐CoA synthase 2 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma

“…We thus speculated that the impact of ACSS2 on invasion and metastasis might be executed through the HIF family, which is considered to play an important role in inducing EMT and metastasis. (36)(37)(38) Previous studies have reported that the acetate/ACSS2 switch could regulate HIF-2a stress signaling (15) and that HIF-2a is more common in chronic hypoxia. (10) Therefore, we focused on both the amount and the activity of HIF-2a.…”

MicroRNA-92a promotes cell viability and invasion in cervical cancer via directly targeting Dickkopf-related protein 3

“…Through interacting with the Wnt signaling pathway, DKK3 has been identified to be involved in various biological processes, including embryonic development and tumorigenesis (27,28). The expression of DKK3 has been indicated to be frequently decreased in various cancers such as pancreatic cancer and breast cancer, and DKK3 has been suggested to function as an important tumor suppressor (19,20). A study by Ryu et al (29) reported that downregulation of DKK3 was associated with adverse clinical outcomes of cervical cancer.…”

“…As DKK3 has been demonstrated to act as a tumor suppressor in various types of human cancer such as pancreatic cancer and breast cancer (19,20), DKK3 may be involved in the miR-92a-induced invasion and cell viability of HeLa cells. To explore this speculation, miR-92a-overexpressing cervical cancer cells were transfected with pcDNA3.1-DKK3 expression plasmid.…”

TGFβ1‐Smad3‐Jagged1‐Notch1–Slug signaling pathway takes part in tumorigenesis and progress of tongue squamous cell carcinoma

“…Chemotherapy drugs can induce EMT in cancer cells. In contrast, EMT can mediate the drug resistance of cancer cells . In the process of tumor progression, cancer cells take part in the process of EMT which is a highly conserved biological mechanism to disguise themselves into the stroma like cancer cells, making it into ‘Wolf in sheep's clothing’.…”