TEC kinase stabilizes PLK4 to promote liver cancer metastasis.

Abstract

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 overexpression 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 PLK4-mediated 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.

• Authors: Sai-Fung Yeung, Yuan Zhou, Wenjun Zou, Wing-Lim Chan, Yick Pang Ching
• Journal: Cancer letters (Cancer Lett) Vol. 524 Pg. 70-81 (01 01 2022) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 34637843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• PLK4 protein, human
• Tec protein-tyrosine kinase
• Protein-Tyrosine Kinases
• Protein Serine-Threonine Kinases

Topics

• Carcinogenesis (genetics)
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Genomic Instability (genetics)
• Humans
• Liver Neoplasms (genetics, pathology)
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Metastasis
• Phosphorylation (genetics)
• Protein Serine-Threonine Kinases (genetics)
• Protein-Tyrosine Kinases (genetics)
• Transcriptome (genetics)