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. 2020 Sep 3;10:1633. doi: 10.3389/fonc.2020.01633

FIGURE 2.

FIGURE 2

The direct and indirect antitumor mechanisms of the somatostatin analogs in meningioma. Somatostatin analogs exert their direct antitumor effects by binding to SSTR2, which leads to the activation of SHP1 and SHP2. SHP2 can further activate SHP1. SHP1 mediates antiproliferative action through inhibiting the PI3K/Akt pathway and induces cell cycle arrest through down-regulating cyclin D1 while up-regulating p27/Kip 1. Suppressing secretion of VEGF and GH/IGF-1 and activating the immune system are involved in indirect antitumor mechanisms of somatostatin analogs. Abbreviations: Akt, protein kinase B; GH, growth hormone; insulin-like growth factor-1 (IGF-1); PI3K, phosphatidylinositol 3-kinase; SHP1, SH2-containing phosphatase-1; SHP2, SH2-containing phosphatase-2; SSTR, somatostatin receptor; and VEGF, vascular endothelial growth factor.