Our study shows that inhibition of ERK1/2 and AKT by PD98059 and LY294002 in HPIP-overexpressing CRC cells attenuates the ability of HPIP to promote CRC cell proliferation and migration and to regulate the expression of the important cell cycle regulators cyclin D1, cyclin A and cyclin B1 as well as the EMT regulators E-cadherin and N-cadherin, suggesting that activation of ERK1/2 and AKT is critical for HPIP modulation of the proliferation and migration of CRC cells and of the expression of cell cycle and EMT regulators. Here, CDH2 is linked to colorectal carcinoma.