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

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.

Comprehensive Analysis Reveals PTK6 as a Prognostic Biomarker Involved in the Immunosuppressive Microenvironment in Breast Cancer

“…Overexpression of GAB1 was able to offset the inhibitory effects of PTK6 knockdown on cervical cancer cells. Cervical cancer cells were protected against the progression of malignant cervical cancer when PTK6 expression was knocked down [ 31 ]. Cagle and his group showed that the overexpression of miR-214 in prostate cancer cells led to the induction of apoptosis, which in turn inhibited cell proliferation and the ability to form colonies.…”

The Role of GAB1 in Cancer

“…In hepatocellular carcinoma cell lines, GAB1 knockdown inhibited cell proliferation by reducing of ERK1/2 activation [ 95 ]. The absence of protein tyrosine kinase 6 (PTK6) expression reduces the proliferative capacity of cervical cancer cells and apoptosis induction in a GAB1-dependent manner [ 96 ]. HCK-mediated phosphorylation of GAB1 induces proliferation and survival in IL-6-induced multiple myeloma cells.…”

“…Furthermore, GAB1 has been described to be upregulated to promote migration in anaplastic thyroid carcinoma cells through modulation of the AKT–Multidrug Resistance Protein 1 (MDR1) axis [ 117 ]. GAB1 overexpression increases migratory and invasive activity in cervical cancer cell lines [ 96 ]. Also, GAB1 has been reported to be closely involved in glioblastoma cell invasion through HGF-induced activation of dedicator of cytokinesis 7 (DOCK7) and RAC1 [ 118 ].…”