FZD2 and its interactions with the cadherins have a role in invasion and metastasis. immunosurveillance is evident in OSCC-GB with the downregulation of CADM1.
We uncover a previously unrecognized inverse relationship with overexpression of a network of important predicted target mRNAs deregulated in HNSCC, that includes key molecules involved in proliferation (EGFR, MET, IGF1R, IRS1, E2F7), differentiation (WNT7B, FZD2), adhesion, and invasion (ITGA6, SERPINE1).
This data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis, a non-canonical WNT pathway for promoting EMT progression, which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.
Concerning the mechanism, gain- and loss-of-function experiments showed the oncogenic action of FZD2 in HCC cell proliferation, apoptosis, migration, and invasion.
In addition, we found that the phosphorylation of signal transducer and activator of transcription-3 (STAT3) was enhanced by Fzd2 overexpression, but suppressed by Fzd2 depletion, and that STAT3‑specific shRNA attenuated Fzd2 overexpression‑induced cell invasion.