RETRACTED ARTICLE: Dickkopf-1 contributes to hepatocellular carcinoma tumorigenesis by activating the Wnt/β-catenin signaling pathway

Abstract

Dysregulation of dickkopf-related protein 1 (DKK1) expression has been reported in a variety of human cancers. We previously reported that DKK1 was upregulated in hepatocellular carcinoma (HCC). However, the role of DKK1 in HCC remains unclear. This study aimed to investigate the clinical significance and biological functions of DKK1 in HCC. The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). DKK1 was silenced or overexpressed in HCC cell lines, and in vitro and in vivo studies were performed. Immunohistochemistry revealed that DKK1 was weakly expressed in cirrhotic tissues (8/22, 36.4%) but upregulated in HCC tissues (48/53, 90.6%, cohort 1). Significant upregulation of DKK1 was observed in 57.6% (19/33, cohort 2) of HCC tissues by qRT-PCR, and the expression of DKK1 was associated with tumor size (P = 0.024) and tumor number (P = 0.019). Genetic depletion of DKK1 impaired the proliferation, colony-forming ability, invasion, and tumor formation of HCC cells (HepG2 and HUH-7). Conversely, forced expression of DKK1 increased the proliferation, colony-forming ability, and invasion of HepG2 and HUH-7 cells in vitro and enhanced tumor formation in vivo. Subsequent investigation revealed that the DKK1-mediated proliferation and tumorigenicity of HepG2 and HUH-7 cells is dependent on the Wnt/β-catenin signaling pathway. These findings indicate that DKK1 plays an oncogenic role in HCC by activating the Wnt/β-catenin signaling pathway.

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

“…1,2 Despite the tremendous progress in HCC treatment, therapeutic options remain limited. 3,4 Only a small proportion of patients with HCC are eligible for curative treatments such as surgical resection, ablation, and liver transplantation. The majority of patients with HCC demonstrate postsurgical recurrence and metastasis, resulting in a poor 5-year overall survival rate.…”

Differences in Clinical Features and Diagnostic Strategies Between IgG4-Related Autoimmune Cholangitis and Cholangiocarcinoma

“…The stained sections were independently evaluated by two investigators who were blind to the clinical data of patients. The immunohistochemical staining sections were first scanned under a light microscope at low magnification (x40), and then five non-overlapping fields were observed at a final magnification of x400 ( 13 , 14 ). The sections were calculated by recording the number of IgG4-positive plasma cells in 10 high-power fields (HPFs, magnification, x400).…”

Biomarkers in Hepatocellular Carcinoma: Current Status and Future Perspectives

“…Others candidates include Apelin [58], β2 microglobulin [59], dickkopf-1 [60], GATA Zinc Finger Domain Containing 1 [61], osteopontin [62] and squalene epoxidase [63] that are reported to have abnormal expressions in HCC as compared to normal control. Although these markers are reported as sensitive biomarkers for HCC prediction, they have not yet been applied in clinical or recommended for use by major professional hepatology societies, probably because of limited sample size, lack of external validation, or sample accessibility, implying the complexity and challenges of biomarker development.…”