Fig. 1

EGFR and PI3K signaling pathways in CRC. The binding of EGF to the extracellular domain of EGFR, induces dimerization, and activation of intrinsic kinase activity. The proteins, those are recruited to active EGFR include a number of Src homology 2 (SH2) proteins. One of the adaptor proteins, GRB2 recruits SOS to the membrane. SOS activates GDP/GTP exchange which recruits RAF to the membrane. RAF phosphorylates MEKs, which then activates the extracellular signal regulated kinase (ERK). Phosphorylated ERK translocates to nucleus and activates transcription factors leading to expression of the target genes such as c-FOS, c-JUN and myc [4]. GRB2 recruits PI3Ks, another major mediator of EGFR signaling pathway. PI3Ks converts PIP2 to PIP3. PIP3 binds to PH domain of AKT and recruits it to plasma membrane. PDK1 phosphorylates AKT which in turn regulates the activity of various proteins that mediate cell survival. Activated AKT inhibits TSC2 via phosphorylation. Inactive TSC1/2 is unable to bind RAS homolog enriched in brain (RHEB), which subsequently enables its activation of mTORC1 at the surface of lysosome. Upon activation, mTORC1 regulates many cellular functions, such as cell growth, protein synthesis and autophagy via S6 kinase (S6K; RPS6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1; EIF4EBP1) [68]