Thus, while decreased KRas, beta-catenin, and TNFα signaling likely underly the attenuation of tumor growth by Hpa2-Nuc in pre-clinical models (Fig. 6), activation of the immune system likely play a suppressive role in breast cancer patients in which nuclear localization of Hpa2 was retained (Fig. 1D). Here, HPSE2 is linked to breast cancer.