Figure 3: The PI3K/AKT signaling in prostate cancer. PI3K/AKT can induce enhanced activation of cancer cells by direct downstream effects. At the same time, this pathway (and downstream target genes) might affect the action of ERKs, which could lead to inhibition of AR-dependent activation, thus favoring an AR-independent growth. Conversely, AR pathway target genes can limit the PI3K/AKT pathway, favoring an AR-dependent tumor growth. A deregulated PI3K pathway (usually due to mutated or null PTEN) can also inhibit the Ras/MEK/ERK pathway, through enhanced activation of AKT. PI3K/AKT can also enhance the presence of stable metalloproteinase receptors (MT1-MMP), which favors invasive and metastatic phenotypes for these tumor cells. TGFβ signaling (through TGFβ3 ligation) can have a dual role in PI3K/AKT in PCa cells; for instance, benign cell lines enhance the expression of AKT and subsequent activation of this pathway following TGFβ3 engagement; malignant cell lines enhance PTEN expression in response to TGFβ3 engagement. Finally, N-cadherin enhanced expression in PCa cells leads to enhanced production of CCL2, which avoids autophagy in part through PI3K/AKT pathway.