SMAD4 and cancer: While Z cell activation for the memory anticancer response does not require pre-exposure of Z cells to the cancer antigens [6], we tested the hypothesis that Zfra4-10 binds to membrane Hyal-2 of spleen Z cells and activates the Hyal-2/WWOX/SMAD4 signaling, which is needed for cytotoxic Z cell activation to kill cancer cells.