SOX2, an amplification target of 3q26.3, promote tumor proliferation via AKT signaling in esophageal cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790339
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: GEN YASUYUKI 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80596156)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 食道癌 / SOX2 / 遺伝子増幅 / AKT / mTOR

Outline of Final Research Achievements

The transcription factor SOX2 is essential for the maintenance of embryonic stem cells and normal development of the esophagus. We have revealed that the SOX2 gene is an amplification target of 3q26.3 in esophageal squamous cell carcinoma (ESCC). To identify the oncogenic activity of SOX2 in ESCC cells, using a phosphoprotein array, we assayed multiple signaling pathways activated by SOX2 and determined that SOX2 activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. LY294002, an inhibitor of phosphatidylinositol 3-kinase, suppressed the ability of SOX2 to enhance proliferation of ESCC cells in vitro. In mouse xenografts, SOX2 promoted in vivo tumor growth of ESCC, which was dependent on AKT/mTORC1 activation. LY294002 suppressed the ability of SOX2 to enhance tumor growth of ESCC. Furthermore, tissue microarray analysis of 61 primary ESCC tumors showed a positive correlation between expression levels of SOX2 and phosphorylated AKT.

Free Research Field

消化器内科