PIK3CA and neoplasm: In the same way, abnormal activation of the PI3K-Akt pathway can be observed by the inhibiting mutations of PTEN and the activating mutations of PIK3CA [24], and IRS-4, which is the upstream activator of Akt pathway, translocates into nucleus in tumor tissues, while IRS-4 is located in the cytosol and membrane in healthy tissues [51].