Calnuc‐derived nesfatin‐1‐like peptide is an activator of tumor cell proliferation and migration

Abstract

Calnuc (nucleobindin1, nucb1) is a Ca2+‐binding protein involved in the etiology of many human diseases. To understand the functions of calnuc, we have identified a nesfatin‐1‐like peptide (NLP) in its N‐terminus that is proteolyzed by a convertase enzyme in the secretory granules of cells. Mutational studies confirm the presence of a proteolytic cleavage site for proprotein convertase subtilisin/kexin type 1 (PCSK1). We demonstrate that NLP regulates Gαq‐mediated intracellular Ca2+ dynamics, likely via a G protein‐coupled receptor. NLP treatment to carcinoma cell lines (SCC131 cells) promotes the expression of regulators of cell cycle, proliferation and clonogenicity by the AKT/mTOR pathway. NLP is causative of augmented migration and epithelial‐mesenchymal transition (EMT), illustrating its metastatic propensity and establishing its tumor promotion ability.