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Soluble LRP6 E1-E2 Wnt receptor to regulate tumor growth and cellular invasion

Title
Soluble LRP6 E1-E2 Wnt receptor to regulate tumor growth and cellular invasion
Other Titles
Wnt수용체 soluble LRP6 E1E2 발현에 따른 종양 형성과 세포의 침습 억제
Issue Date
2012
Publisher
Graduate School, Yonsei University
Description
Dept. of Medical Science/박사
Abstract
Aberrant activation of the Wnt pathway contributes to human cancer progression. Antagonists that interfere with Wnt ligand/receptor interactions can be useful in cancer treatments. In this study, we evaluated the therapeutic potential of a soluble Wnt receptor decoy in cancer gene therapy. We designed a Wnt antagonist sLRP6E1E2, and generated a replication-incompetent adenovirus (Ad), dE1-k35/sLRP6E1E2, and a replication-competent oncolytic Ad, RdB-k35/sLRP6E1E2, both expressing sLRP6E1E2. sLRP6E1E2 prevented Wnt-mediated stabilization of cytoplasmic -catenin, decreased Wnt/-catenin signaling and cell proliferation via the mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. sLRP6E1E2 induced apoptosis, Cytochrome c release, and increased cleavage of PARP and caspase-3. sLRP6E1E2 suppressed growth of the human tumor xenograft, reduced motility and invasion of cancer cells. In addition, sLRP6E1E2 upregulated expression of epithelial marker genes, while sLRP6E1E2 downregulated mesenchymal and differentiation markers genes. Taken together, sLRP6E1E2, by inhibiting interaction between Wnt and its receptor, suppressed Wnt-induced cell proliferation and epithelial-to-mesenchymal transition
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/134324
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
Yonsei Authors
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