In order to further examine the role of nuclear Hpa2 in breast cancer, we engineered a Hpa2 gene construct in which the signal peptide of Hpa2 (amino acids 1–38; see “Materials and methods” section) was removed, and a nuclear localization sequence (NLS) was introduced at the protein C-terminus (Hpa2-Nuc; Supplementary Fig. 1D, upper panel). Here, NUCB1 is linked to breast cancer.