Wnt5a-induced docking of Plk1 on HEF1 promotes HEF1 translocation and tumorigenesis

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Title
Wnt5a-induced docking of Plk1 on HEF1 promotes HEF1 translocation and tumorigenesis
Author(s)
Jeong Ah Hwang; Ji Eun Yu; Sun Ok Kim; Dong Hyun Kim; K S Cho; Kyung Ho Lee
Bibliographic Citation
Genes & Genomics, vol. 43, no. 5, pp. 567-575
Publication Year
2021
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.
Keyword
Wnt5aPlk1HEFFocal adhesionTumorigenesis
ISSN
1976-9571
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s13258-021-01088-x
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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