PI3K/AKT kwown as protein kinase B that promote cell

PI3K/AKT pathway is one of the utmost
mechanisms which involved with intracellular signal transduction. Numerous
kinds of membrane receptors are functional in cell proliferation, survival and
angiogenesis, especially tyrosine kinase growth factor receptors like
endothelial growth factor receptors (EGFR), G protein-coupled receptors (GPCR)
and cell adhesion molecules (Ramalingam, Ramamurthy and Njar, 2017) have to be
triggered. PI3K helps to catalyse the phosphorylation process, transfer of
phosphate group to phosphatidylinositol-4,5bisphosphate (PIP2) and further
converted into phosphatidylinositol-3,4,5 trisphosphate (PIP3). PIP3 is able to
bind with AKT, causing the formation of activated AKT via phosphorylation. This
activated complex make some proteins associated with mammalian target of
rapamycin (mTOR) was excited, which responsible to regulate many types of
cellular responses (Vara et al., 2004). In brief, PIP3 functions as second
messenger (Tomlins, Rubin and Chinnaiyan, 2006) that activates AKT or also
kwown as protein kinase B that promote cell growth, invasion rate and
angiogenesis. Thus, the presence of PTEN is to suppress PI3K/AKT signalling
pathway by ceasing its activity. They can dephosporylate the PIP3 and become
PIP2 through the effect of negative regulation. With the aid of neutral
endopeptidase (NEP), the binding are strong sufficiently for PTEN stabilization
(Tomlins, Rubin and Chinnaiyan, 2006). Therefore, PTEN is a tumor suppressor.
When the expression of PTEN is lost, it will cause the hyperactive or
amplification in PI3K/AKT pathway which escalates the activity in prostate
cancer development as the dephosphorylation from PIP3 to PIP2 (Vara et al.,
2004) cannot be done. Additionally, cross-talking always present among the
pathways such as AR and PI3K/AKT signalling. Thus, aberrant PI3K/AKT pathway
will directly affect the AR signalling route, halting the Ras/MEK/ERK pathway
through activation of amplified AKT (Ramalingam, Ramamurthy and Njar, 2017). On
the other hands, Myc, the downstream PI3K/AKT target interacts with AKT also
give rise to the prostate cancer development and progression (Ramalingam,
Ramamurthy and Njar, 2017).