Background: Tankyrase1 (TNKS1), which often shows abnormal expression in many malignant tumor cells, plays an important role in tumor progression. In our previous study, we found that TNKS1 is also closely related to pathologic grade in human astrocytoma and its expression level is positively correlated with the Wnt/β-catenin pathway. This study is aimed to further elucidate the biological functions of TNKS1 as well as its relationship with the Wnt/β-catenin pathway.
Methods: TNSK1 overexpression and knockdown vectors were constructed and transfected into glioblastoma cell lines U251 MG and U87, respectively. Viability, apoptosis, cell cycle and cell invasiveness in the treated cells were investigated.
Results: In comparison with untreated cells, U251 and U87 cells overexpressing TNSK1 showed significantly increased cell viability and decreased apoptosis, while the TNKS1 knockdown U251 and U87 cells had reduced cell invasive ability and increased apoptosis, respectively. In addition, immunoprecipitation study showed that TNKS1 could be detected by β-catenin antibody after pull-down, indicating that TNKS1 directly interacts with β-catenin, further indicating that TNKS1 could be regarded as a positive regulator of the Wnt/β-catenin pathway in astrocytoma. Moreover, knockdown of TNKS1 in U251 and U87 cells also leads to suppressed Wnt/β-catenin signaling, and subsequent decrease of cell growth and proliferation, reduced invasion ability and increased apoptosis.
Conclusion: Our findings suggest that TNKS1 might be a potential new therapeutic target for human astrocytoma in gene therapy.
Keywords: TNKS1, Wnt/β-catenin, astrocytoma, U251, U87, siRNA, ADP, diphosphate