Dysregulated APLN have been widely reported in tumorigenesis, yet the role of the proteolytic cleavage of APLN precursor proAPLN in oncogenesis is not known. Here, we identify Furin the unique proprotein convertase able to cleave proAPLN in cancer cells. We generated for preclinical development APLN-DM peptide following alteration of proAPLN cleavage sites. The proteomic analysis was designed to identify dysregulated proteins in APLN and APLN-DM-expressing cells.