Role of pi3k/akt/mtor signaling pathway in induction of epithelial-mesenchymal transition (emt) process and metastasis

Metastasis to main organs such as the liver, lung, brain, and skeleton is responsible for most of cancer deaths. Diagnosing with metastatic cancer have a poor prognosis, with a 10-year survival rate of only 5- 10%. Currently there are no clinically proven drugs for curative purposes of metastatic disease and the treatment regimens have unfortunately not improved for the last 40 years. The mechanisms underlying the metastatic spread of cancer, including the orchestrated programs coordinating cell migration and dissemination throughout disease progression, remain unclear. Several studies have been reported Epithelial-mesenchymal transition (EMT) process as an important mechanism in migration and metastasis of tumor cells. EMT is a highly conserved, fundamental biological process and mostlyreversible phenotype that regulates morphogenesis in multicellular organisms. EMT allows the epithelial cell to undergo substantial biochemical alteration and to achieve mesenchymal phenotypes, such as increased migratory capacity, invasiveness, and resistance to anoikis. Accumulation studies revealed that intracellular cascades PI3K/Akt, MAPK, and Rho GTPases are key signaling mediators to activatethe EMT inducing transcription factors. One of the well-known signaling cascades is The PI3K/Akt/mTOR signaling pathway that is involved in a significant fraction of human tumors promoting cancer cell growth, metabolism, and survival. There are good pieces of evidence that show activation of the PI3K/AKT/mTOR pathway is emerging as a central feature of EMT. Phosphorylation and Activation of AKT as a protein kinase has been shown to phosphorylate and activate some transcription factors, which repress E-cadherin expression and induce EMT.Taken together, EMT is a key process in metastasis of tumor cells, which drive them toward dedifferentiated and mesenchymal form. The growing appreciation of the role AKT and mTOR in metastasis and EMT is leading to many focuses on using of their inhibitors, such as rapamycin, in inhibition of EMT and metastasis. Therefore, suggested these signaling pathways as a good treatment target in inhibition of metastasis and invasion in tumor cells.

کلیدواژه ها:

Cancer Prevention ، Gene and Cancer ، Cancer Treatment and Management ، Targeted Cancer Therapy ، Drugs and Cancer