Abstract 3525: SOX2 promotes tumor growth via activation of the PI3K/Akt/mTORC1 signaling pathway in esophageal squamous cell carcinoma

Our previous study revealed that SOX2, a master regulator during embryogenesis, is an amplification target of 3q26.3 in esophageal squamous cell carcinoma (ESCC) and that SOX2 promotes ESCC cell proliferation. To identify the mechanisms by which SOX2 promotes proliferation of ESCC cells, we assayed multiple signaling pathways activated by SOX2 using a phosphoprotein array. We determined that SOX2 activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Immunoblotting confirmed that SOX2 elevated levels of p-AKT and levels of p-p70S6K and p-4E-BP1 which are direct targets of mTORC1. Effects of SOX2 knockdown, including reduced levels of p-AKT and decreased ESCC cell viability, were reversed with constitutive activation of AKT with PTEN knockdown. SOX2 also promoted in vivo tumor growth of ESCC with AKT/mTORC1 activation in mouse xenografts. LY294002, a PI3K inhibitor, suppressed the ability of SOX2 to enhance tumor growth of ESCC by reducing cell proliferation. Furthermore, tissue microarray analysis showed a positive correlation between expression levels of SOX2 and p-AKT in 61 primary ESCC tumors. Our results suggest that SOX2 promotes ESCC tumor growth via activation of the PI3K/AKT / mTORC1 signaling pathway, which enhances cell proliferation. Citation Format: Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Akira Tomie, Yoshito Ito. SOX2 promotes tumor growth via activation of the PI3K/Akt/mTORC1 signaling pathway in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3525. doi:10.1158/1538-7445.AM2014-3525