國家衛生研究院 NHRI:Item 3990099045/14969
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    題名: GSKIP modulates cell aggregation through EMT/MET signaling rather than differentiation in SH-SY5Y human neuroblastoma cells
    作者: Tsai, CY;Ko, HJ;Chiou, SJ;Lin, XY;Chuang, TH;Cheng, JT;Su, YF;Loh, JK;Hong, YR
    貢獻者: Immunology Research Center
    摘要: GSK3β interacting protein (GSKIP) is a small A-kinase anchor protein previously reported to mediate the N-cadherin/β-catenin pool for differentiation in SH-SY5Y cells through overexpression of GSKIP to present the neuron outgrowth phenotype. To further investigate how GSKIP functions in neurons, CRISPR/Cas9 technology was utilized to knock out GSKIP (GSKIP-KO) in SH-SY5Y. Several GSKIP-KO clones resulted in an aggregation phenotype and reduced cell growth without retinoic acid (RA) treatment. However, neuron outgrowth was still observed in GSKIP-KO clones treated with RA. The GSKIP-KO clones exhibited an aggregation phenotype through suppression of GSK3β/β-catenin pathways and cell cycle progression rather than cell differentiation. Gene set enrichment analysis indicated that GSKIP-KO was related to epithelial mesenchymal transition/mesenchymal epithelial transition (EMT/MET) and Wnt/β-catenin/cadherin signaling pathways, suppressing cell migration and tumorigenesis through the inhibition of Wnt/β-catenin mediated EMT/MET. Conversely, reintroduction of GSKIP into GSKIP-KO clones restored cell migration and tumorigenesis. Notably, phosphor-β-catenin (S675) and β-catenin (S552) but not phosphor-β-catenin (S33/S37/T41) translocated into the nucleus for further gene activation. Collectively, these results suggested that GSKIP may function as an oncogene to form an aggregation phenotype for cell survival in harsh environments through EMT/MET rather than differentiation in the GSKIP-KO of SH-SY5Y cells. GSKIP Implication in Signaling Pathways with Potential Impact on SHSY-5Y Cell Aggregation.
    日期: 2023-09
    關聯: Journal of Cell Communication and Signaling. 2023 Sep;17(3):1039-1054.
    Link to: http://dx.doi.org/10.1007/s12079-023-00752-z
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1873-9601&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000981840200001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85158171353
    顯示於類別:[莊宗顯] 期刊論文

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