We generated ApcMin/+ mice with selective deletion of EP4 receptors in myeloid cells and found that selective EP4 deletion in myeloid cells effectively reduced adenoma number and size in ApcMin/+ mice in association with inhibition of adenoma activities of ERK, PI3K, PDK1, AKT, mTOR and its downstream targets, p60 S6K and eIF-4B and rpS6. Here, PDK1 is linked to adenoma.