PYY modulates the tumorigenesis and progression of colorectal cancer unveiled by proteomics.

Despite decrease in mortality caused by colorectal cancer (CRC), there remains no effective therapeutic method for patients with CRC. We attempted to screen biomarkers with therapeutic values in CRC. Proteomic analysis was performed on tumor, tumor-adjacent, and normal tissues derived from five patients with colon adenocarcinoma (COAD) via label-free proteome profiling. Differentially expressed proteins (DEPs) were identified, and functional annotation was performed based on the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The effect of marker proteins on CRC was determined via cell function experiments and using tumor organoid models. The localization of the marker proteins was determined via immunofluorescence. A total of 126 DEPs were identified in COAD tissues compared with normal tissues, of which Peptide YY (PYY) overlapped among the tumor, adjacent, and normal groups. DEPs in the cancer group vs. normal group were enriched in the regulation of cell cycle checkpoint, developmental process, focal adhesion, and apoptosis-related pathways. The low expression of PYY in CRC tissues was verified via qRT-PCR, western blotting, and immunohistochemistry. Overexpression of PYY promoted apoptosis and inhibited the proliferation, migration, and invasion of HCT116 and HT29 cells. Furthermore, PYY was secreted by neurons and its supplementation suppressed tumor organoid growth in a dose-dependent manner. In conclusion, PYY exerted inhibitory action on CRC and could be a therapeutic target for CRC.