|Title:||The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells||Authors:||LI-HAN CHEN||Issue Date:||2018||Publisher:||Springer Nature||Journal Volume:||7||Journal Issue:||12||Start page/Pages:||95||Source:||Oncogenesis||Abstract:||
Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells. ? 2018, The Author(s).
|URI:||https://scholars.lib.ntu.edu.tw/handle/123456789/561624||DOI:||10.1038/s41389-018-0105-z||metadata.dc.subject.other:||Fas associated death domain protein; semaphorin; semaphorin 6A; unclassified drug; animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; cancer growth; cancer inhibition; cell proliferation; cell survival; coculture; controlled study; cytosol; extracellular space; gene overexpression; gene silencing; human; human tissue; immunoprecipitation; in vitro study; in vivo study; intracellular signaling; lung cancer; lung fibroblast; male; mouse; nonhuman; pleiotropy; priority journal; protein binding; protein domain; protein function
|Appears in Collections:||漁業科學研究所|
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