Faculty Collaboration Database

FOXP4-mediated induction of PTK7 activates the Wnt/β-catenin pathway and promotes ovarian cancer development. Cell Death Dis 2024 May 13;15(5):332

Date

05/14/2024

Pubmed ID

38740744

Pubmed Central ID

PMC11091054

DOI

10.1038/s41419-024-06713-7

Scopus ID

2-s2.0-85192951272 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Author List

Ji J, Qian Q, Cheng W, Ye X, Jing A, Ma S, Ding Y, Ma X, Wang Y, Sun Q, Wang X, Chen Y, Zhu L, Yuan Q, Xu M, Qin J, Ma L, Yang J, Zhang M, Geng T, Wang S, Wang D, Song Y, Zhang B, Xu Y, Xu L, Liu S, Liu W, Liu B

Author

Wei Liu PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Adhesion Molecules
Cell Line, Tumor
Cell Proliferation
Female
Forkhead Transcription Factors
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
Ovarian Neoplasms
Receptor Protein-Tyrosine Kinases
Wnt Signaling Pathway
beta Catenin