Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide, characterized with high heterogeneity and inclination to metastasize. Emerging evidence suggests that BAP31 gets involved in cancer progression with different kinds. It still remains unknown whether and how BAP31 plays a role in HCC metastasis. Epithelial–mesenchymal transition (EMT) has been a common feature in tumor micro-environment, whose inducer TGF-β increased BAP31 expression in this research. Elevated expression of BAP31 was positively correlated with tumor size, vascular invasion and poor prognosis in human HCC. Ectopic expression of BAP31 promoted cell migration and invasion while BAP31 knockdown markedly attenuated metastatic potential in HCC cells and mice orthotopic xenografts. BAP31 induced EMT process, and enhanced the expression level of EMT-related factor Snail and decreased contents and membrane distribution of E-cadherin. BAP31 also activated AKT/β-catenin pathway, which mediated its promotional effects on HCC metastasis. AKT inhibitor further counteracted the activated AKT/β-catenin/Snail upon BAP31 over-expression. Moreover, silencing Snail in BAP31-overexpressed cells impaired enhanced migratory and invasive abilities of HCC cells. In HCC tissues, BAP31 expression was positively associated with Snail. In conclusion, BAP31 promotes HCC metastasis by activating AKT/β-catenin/Snail pathway. Thus, our study implicates BAP31 as potential prognostic biomarker, and provides valuable information for HCC prognosis and treatment.
We investigated whether or not there are autoantibodies for DKK1 (Dickkopf-1) in patients with non-small cell lung cancer (NSCLC) and whether this autoantibody can be used for cancer detection.The levels of DKK1 autoantibodies were determined in 93 NSCLC patients and 87 healthy controls.We found that, in the sera, the presence of autoantibody against DKK1 was highly correlated with NSCLC. High anti-DKK1 autoantibody titres were found in the sera of NSCLC patients, whereas low or negative titres were found in the control group. The ROC curve results showed that autoantibody immunoassay exhibited 62% sensitivity and 84% specificity. The sensitivity for the detection of NSCLC in stage I also reach 64.3%. Furthermore, a combined ELISA assays for both DKK1 and autoantibody DKK1 increased sensitivity and classified 81.7% (76/93) of the NSCLC patients as positive, whereas only 13.8 % (12/87) of healthy volunteers were falsely diagnosed as positive.Our results suggest that the detection of circulating DKK1 autoantibody could potentially serve as a useful non-invasive marker for determining lung cancer status.
Background: Emerging evidence suggests that Eph/ephrin-system involves different facets of tumorigenesis and cancer progression. Whether ephrin-A3, a cognate ligand to several Eph receptors, plays a role in HCC cell proliferation and metastasis remains unclear.Methods: The expression of ephrin-A3 was detected by immunohistochemistry and qRT-PCR in human HCC tissues. The clinical significance of ephrin-A3 was analyzed using multiple databases. The biological functions of ephrin-A3 were investigated in vitro and in vivo. Immunofluorescence and co-immunoprecipitation were used to detect the interaction between ephrin-A3 and EphA2.Findings: Elevated expression of ephrin-A3 was positively correlated with the histological grade, metastasis and poor prognosis in human HCC. Knockdown of ephrin-A3 led to significantly decreased proliferative activity and metastatic potential, and re-introduction of ephrin-A3 rescued the decreased proliferation, migration, and invasion induced by ephrin-A3 knockdown in HCC cells. Ephrin-A3 interacted with EphA2 and positively regulated EphA2 and AKT phosphorylation. Knockdown of EphA2 attenuated HCC cell proliferation, migration, and invasion induced by ephrin-A3 overexpression. Furthermore, ephrin-A3-induced EphA2 phosphorylation is both a substrate and a positive regulator of AKT. In HCC tissues, ephrin-A3 expression was positively correlated with EphA2, and patients with high co-expression of ephrin-A3 and EphA2 exhibited poorer prognosis.Interpretation: Ephrin-A3 promotes HCC metastasis by interacting with EphA2 and activating EphA2 and AKT. Thus, our study implicates ephrin-A3 and EphA2 as potential prognostic biomarkers, and provides valuable information for HCC prognosis and treatment.Funding Statement: This work was supported in part by grants from the National Natural Science Foundation of China (81672832), Outstanding Subject Leader Training Program of Shanghai Municipal Commission of Health and Family Planning (2018BR20), the National Natural Science Foundation of Shanghai (20ZR1454000), the National Key Sci-Tech Special Project of China (2018ZX10723204-006), the Research Project of Shanghai Municipal Commission of Health and Family Planning (20204Y0093), and the Grants from the State Key Laboratory of Oncogenes and Related Genes (91-17-18).Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: The study was approved by the Research Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine, and informed consent was obtained from each patient from the Zhejiang University (Hangzhou, China) and the Qidong Liver Cancer Institute (Qidong, China).
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