Promotion of Epithelial-mesenchymal Transition by Frizzled2 is Involved in the Metastasis of Endometrial Cancer
Affiliations
The Wnt signaling pathway is essential for embryonic development, and genetic alteration in this network is closely correlated with tumorigenesis and progression. Previous research has shown that Wnt receptor Frizzled2 (Fzd2) is elevated in many metastatic cancer cell lines and high grade tumors. Yet, little is known about the Fzd2 expression and activity in human endometrial cancer (EC). In this study, we present evidence of a direct role of Fzd2 in human EC. We found that Fzd2 expression was higher in EC than that in adjacent normal tissues, and was correlated with epithelial‑mesenchymal transition markers. Next, it was determined that the stable overexpression of Fzd2 in HEC-1B and Ishikawa cells promoted cell migration and induced an EMT phenotype. Conversely, RNA interference-mediated depletion of Fzd2 inhibited EC cell migration. Additionally, mechanistic investigation revealed that elevated Fzd2 expression activated canonical Wnt signaling and was blocked by canonical Wnt signaling inhibitor XAV939. However, Fzd2 did not influence the proliferation of EC cells. Thus, Fzd2 may be a potential marker for EC metastasis and a target for future therapies for this disease.
Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.
Liu H, Sun X, Xiu S, Zhang X, Wang Z, Gu Y Acta Pharmacol Sin. 2024; 45(8):1556-1570.
PMID: 38632318 PMC: 11272778. DOI: 10.1038/s41401-024-01270-3.
Marshall A, Kommoss K, Ortmann H, Kirchner M, Jauckus J, Sinn P Reprod Biol Endocrinol. 2023; 21(1):33.
PMID: 37005590 PMC: 10067221. DOI: 10.1186/s12958-023-01083-9.
Ledinek Z, Sobocan M, Sisinger D, Hojnik M, Budefeld T, Potocnik U Front Oncol. 2023; 13:1013463.
PMID: 36969079 PMC: 10031053. DOI: 10.3389/fonc.2023.1013463.
A comprehensive characterization of the transcriptome in enzalutamide resistance prostate cancer.
Wang L, Peng Y, Dong S, Hou D, Li N, Li H Ann Transl Med. 2022; 9(24):1782.
PMID: 35071476 PMC: 8756251. DOI: 10.21037/atm-21-6191.
De P, Aske J, Dale A, Espaillat L, Starks D, Dey N Am J Transl Res. 2021; 13(11):12168-12180.
PMID: 34956444 PMC: 8661239.