Related Experiment Videos
TFAP2A-driven PTK6 promotes endometrial cancer progression through activation of the MEK/ERK signaling pathway
Aqiang Zhu1, Yangyang Rao1, Qiaofan Xia2
1Department of Gynecology, The Affiliated Xuancheng Hospital of Wannan Medical University (People's Hospital of Xuancheng), Anhui Province, China.
Background:
Endometrial cancer is an immune-responsive gynecological malignancy, but biomarkers linking oncogenic signaling with the tumor immune microenvironment remain limited. Protein tyrosine kinase 6 (PTK6), a non-receptor tyrosine kinase involved in tumor progression, remains insufficiently defined in endometrial cancer.
Methods:
Public transcriptomic and proteomic datasets were analyzed to evaluate PTK6 expression, prognosis, and pathway enrichment. Exploratory transcriptomic analyses examined associations between PTK6 expression and immune-related features. PTK6 protein expression was validated in clinical specimens by western blotting and immunohistochemistry. Gain- and loss-of-function experiments were performed to assess PTK6-mediated effects on cell proliferation, migration, and EMT-associated marker expression in vitro, and on subcutaneous xenograft tumor growth in vivo. The relationship between PTK6 and MEK/ERK signaling was examined by enrichment analysis, western blotting, and pharmacological inhibition. TFAP2A-mediated transcriptional regulation of PTK6 was investigated using JASPAR prediction, qRT-PCR, western blotting, and dual-luciferase reporter assays.
Results:
PTK6 was significantly upregulated in endometrial cancer and associated with poor overall survival. PTK6 knockdown inhibited cell proliferation and migration and altered EMT-associated marker expression in vitro. Subcutaneous xenograft experiments showed that PTK6 knockdown reduced tumor growth, whereas PTK6 overexpression enhanced tumor growth. PTK6 expression was associated with RAS/MEK/ERK pathway activation, and PTK6 inhibition reduced cell viability, migration, and MEK/ERK phosphorylation. Exploratory analyses of public transcriptomic datasets revealed associations between PTK6 expression and immune-related signatures. TFAP2A transcriptionally activated PTK6 and enhanced PTK6-driven tumor-promoting effects.
Conclusion:
PTK6 promotes EC cell proliferation and migration in vitro and subcutaneous tumor growth in vivo. The findings implicate the TFAP2A/PTK6/MEK/ERK axis in EC progression and suggest PTK6 as a potential therapeutic target.
Related Concept Videos
MAPK Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Mitogens and the Cell Cycle
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Abnormal Proliferation