AI Article Synopsis
- The study investigates how the upregulation of HEF1 and Plk1 contributes to cancer metastasis and tumor formation.
- The authors reveal that the binding of Wnt5a to Plk1 is essential for HEF1 to move to focal adhesions, which is crucial for cancer cell migration.
- The findings highlight a specific pathway involving Wnt5a and suggest potential new approaches for cancer treatment by targeting this molecular mechanism.
Article Abstract
Background: Upregulation of human enhancer filamentation 1 (HEF1/NEDD9/Cas-L) and Polo-like kinase 1 (Plk1) is closely correlated with metastasis of human cancer. However, the mechanism by which the overexpression of HEF1 or Plk1 stimulates cancer metastasis and induces tumorigenesis remains enigmatic. In addition, the accumulation of HEF1 at the focal adhesion (FA) is known to be an essential event in cancer cell migration, but the mechanism of how HEF1 is targeted to the FA remains yet to be unveiled.
Objective: This study was performed to elucidate the FA docking mechanism of HEF1 and to determine its effect on tumorigenesis.
Methods: To confirm the effect of the kinase on HEF1 translocation, various expression-knockdown stable cell lines were generated using a lentivirus system, and the effect of the HEF1-Plk1 complex on tumorigenesis was confirmed using a xenograft mouse model.
Results: Here, we show that Wnt5a-dependent Plk1 binding to HEF1 is critically required for HEF1 translocation to the FA. We also confirmed that Plk1 and CK1δ activities essential for HEF1 translocation are induced by Wnt5a. Finally, we confirmed the induction of tumorigenesis by the HEF1-Plk1 complex in the xenograft mouse model.
Conclusion: Our data collectively unveil the Wnt5a-CK1δ-HEF1-Plk1-FA remodeling pathway that governs HEF1 transportation to the FA to induce cell migration and tumorigenesis. This study sheds light on a mechanism underlying tumorigenesis and provides new strategies for anticancer therapy.
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| http://dx.doi.org/10.1007/s13258-021-01088-x | DOI Listing |
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