Pan-cancer investigation reveals mechanistic insights of planar cell polarity gene in carcinogenesis.

The fuzzy planar cell polarity protein (Fuz) is an effector component of the planar cell polarity (PCP) signaling. Together with other core and effector proteins, the PCP pathway controls polarized cell movements. Fuz was also reported as a negative regulator of cell survival. In this study, we performed a pan-cancer survey to demonstrate the role of Fuz in multiple types of cancer. In head-neck squamous cell carcinoma and lung adenocarcinoma tumor samples, a reduction of transcript expression was detected. This coincides with the poor overall survival probabilities of these patients. We further showed that promoter hypermethylation contributes to its transcriptional downregulation. Meanwhile, we also identified a relatively higher mutation frequency at the 404 arginine amino acid residue in the coding sequence of locus, and further demonstrated that mutant Fuz proteins perturb the pro-apoptotic function of Fuz. In summary, our study unveiled an intriguing relationship between dysregulation and cancer prognosis, and further provides mechanistic insights of Fuz's involvement in carcinogenesis.