Open AccessPan-cancer investigation reveals mechanistic insights of planar cell polarity gene Fuz in carcinogenesis
Author(s) -
Zhefan Stephen Chen,
Xiao Lin,
Ting-Fung Chan,
Ho Yin Chan
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202582
Subject(s) - carcinogenesis , polarity (international relations) , cancer , biology , cell , gene , microbiology and biotechnology , computational biology , cancer research , genetics
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 Fuz transcript expression was detected. This coincides with the poor overall survival probabilities of these patients. We further showed that Fuz promoter hypermethylation contributes to its transcriptional downregulation. Meanwhile, we also identified a relatively higher mutation frequency at the 404 th arginine amino acid residue in the coding sequence of Fuz locus, and further demonstrated that mutant Fuz proteins perturb the pro-apoptotic function of Fuz. In summary, our study unveiled an intriguing relationship between Fuz dysregulation and cancer prognosis, and further provides mechanistic insights of Fuz’s involvement in carcinogenesis.