TEC kinase stabilizes PLK4 to promote liver cancer metastasis

Aberrated PLK4 expression has been reported in different malignancies and causes centrosome amplification, aneuploidy, and genomic instability. However, the mechanism by which PLK4 is regulated in carcinogenesis remains not fully characterised. Here, we showed that PLK4 was overexpressed in human HCC and over expression of PLK4 predicted poorer patient prognosis. Unexpectedly, we found that induced expression of PLK4 promotes, but knockdown of PLK4 inhibits, HCC cell migration and invasion. Mechanistically, we found that TEC tyrosine kinase, which also promotes HCC cell migration, stabilizes PLK4 by phosphorylation. TEC directly phosphorylates PLK4 at tyrosine 86 residue, which not only stabilizes the protein but also enhances PLK4mediated HCC cell invasion. Further investigation by transcriptome sequencing indicated that PLK4 promotes the phosphorylation of focal adhesion kinase to regulate the focal adhesion pathway in HCC cell migration. Taken together, our results demonstrated that PLK4 plays an important role in HCC metastasis and revealed for the first time the mechanism by which PLK4 promotes HCC metastasis via TEC phosphorylation.

Automated summary

Aberrant expression of PLK4 has been linked to various malignancies with implications in centrosome amplification, aneuploidy, and genomic instability. It has been found that overexpression of PLK4 in human HCC is associated with poor patient prognosis, and induced expression of PLK4 can promote the migration and invasion of HCC cells. Additionally, TEC tyrosine kinase phosphorylates PLK4 to stabilize the protein and enhance HCC cell invasion.