Indeed, we found that in CCAR2-depleted cells also the expression of IGFBP5, PPARG and PDGFA is altered and all these proteins can directly or indirectly regulate AKT activation.16, 28, 29, 30 Moreover, it was previously shown that CCAR2 regulates breast and colon cancer progression by acting respectively as PEA3 and PROX-1 transcription factors co-activator7, 17 and, of note also these proteins are implicated in AKT pathway regulation.31, 32. Here, PROX1 is linked to malignant colon neoplasm.