Interference of PTK6/GAB1 signaling inhibits cell proliferation, invasion, and migration of cervical cancer cells

Mol Med Rep. 2022 Sep;26(3):284. doi: 10.3892/mmr.2022.12800. Epub 2022 Jul 27.

Abstract

Protein tyrosine kinase 6 (PTK6) has shown important cancer‑promoting effects in a variety of cancer types. Nonetheless, its vital role in cervical cancer has not been completely elucidated. The present study sought to address whether PTK6 is involved in the malignant progression of cervical cancer via its interaction with GRB2‑associated binding 1 (GAB1). Western blotting was used to examine PTK6 and GAB1 expression levels. Cell Counting Kit‑8, Transwell, wound healing, and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assays were performed to estimate the corresponding proliferative, migratory, invasive, and apoptotic abilities of the cells. Co‑immunoprecipitation (Co‑IP) assays confirmed binding of PTK6 to GAB1. The results revealed that the expression levels of PTK6 and GAB1 were markedly increased in cervical cancer cell lines compared with those noted in normal cervical epithelial cells. The cell proliferative, invasive, and migratory activities of cervical cancer cells were reduced in the absence of PTK6 expression, whereas the induction of apoptosis was aggravated under these conditions. The results of the Co‑IP assay indicated that PTK6 expression was positively associated with GAB1. In addition, the suppressive effect of PTK6 silencing on the malignant phenotypes of cervical cancer cells was reversed following overexpression of GAB1. In summary, the present study indicated that knockdown of PTK6 expression protected against the malignant progression of cervical cancer, while overexpression of GAB1 counteracted the inhibitory effects of PTK6 knockdown on cervical cancer cells.

Keywords: GRB2‑associated binding 1; apoptosis; cervical cancer; invasion; migration; protein tyrosine kinase 6.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Female
  • Humans
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Protein-Tyrosine Kinases* / genetics
  • Protein-Tyrosine Kinases* / metabolism
  • Signal Transduction
  • Uterine Cervical Neoplasms* / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • GAB1 protein, human
  • Neoplasm Proteins
  • Protein-Tyrosine Kinases
  • PTK6 protein, human

Grants and funding

The present study was supported by the Shenzhen Nanshan District Technology Research and Development and Creative Design Project (grant no. 2020030).