Autophagy related RHEB-CSF1R complex promotes tumor metastasis via advancing phosphorylation levels of PI3K, AKT, mTOR in pancreatic cancer

Figure 11  Proposed mechanism of Ras homolog enriched in brain-mediated cell metastasis in pancreatic cancer. A summary of significant results shows the following: (1) Ras homolog enriched in brain (RHEB) expression is upregulated in pancreatic cancer in vivo and in vitro experiments. It is associated with poor prognosis in our clinical samples and the The Cancer Genome Atlas database; (2) RHEB forms a complex with colony stimulating factor 1 receptor and inhibits autophagy by advancing phosphorylation levels of phosphatidylinositol 3-kinase, AKT serine/threonine kinase 1, and mammalian target of rapamycin; and (3) RHEB-colony stimulating factor 1 receptor complex may promote pancreatic cancer metastasis by upregulating the expression of epithelial-mesenchymal transformation markers N-cadherin and vimentin and downregulating E-cadherin expression via autophagy inhibitors. RHEB: Ras homolog enriched in brain; CSF1R: Colony stimulating factor 1 receptor; PI3K: Phosphatidylinositol 3-kinase; AKT: AKT serine/threonine kinase 1; mTOR: Mammalian target of rapamycin; E-cad: E-cadherin; N-cad: N-cadherin.