國家衛生研究院 NHRI:Item 3990099045/5049
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    题名: Secreted heat shock protein 90alpha induces colorectal cancer cell invasion through CD91/LRP-1 and NF-kappaB-mediated integrin alpha(V) expression
    其它题名: Secreted heat shock protein 90α induces colorectal cancer cell invasion through CD91/LRP-1 and NF-κB-mediated integrin αV expression
    作者: Chen, JS;Hsu, YM;Chen, CC;Chen, LL;Lee, CC;Huang, TS
    贡献者: National Institute of Cancer Research
    摘要: HCT-8 colon cancer cells secreted heat shock protein 90 alpha (HSP90 alpha) and had increased invasiveness upon serum starvation. The concentrated conditioned medium of serum-starved HCT-8 cells was able to stimulate the migration and invasion of non-serum-starved cells, which could be prevented by treatment with an anti-HSP90 alpha antibody. Recombinant HSP90 alpha (rHSP90 alpha) also enhanced HCT-8 cell migration and invasion, suggesting a stimulatory role of secreted HSP90 alpha in cancer malignancy. HSP90 alpha binding to CD91 alpha and Neu was evidenced by the proximity ligation assay, and rHSP90 alpha-induced HCT-8 cell invasion could be suppressed by the addition of anti-CD91 alpha or anti-Neu antibodies. Via CD91 alpha and Neu, rHSP90 alpha selectively induced integrin alpha(V) expression, and knockdown of integrin alpha(V) efficiently blocked rHSP90 alpha-induced HCT-8 cell invasion. rHSP90 alpha induced the activities of ERK, PI3K/Akt, and NF-kappa B p65, but only NF-kappa B activation was involved in HSP90 alpha induced integrin alpha(V) expression. Additionally, we investigated the serum levels of HSP90 alpha and the expression status of tumor integrin alpha(V) mRNA in colorectal cancer patients. Serum HSP90 alpha levels of colorectal cancer patients were significantly higher than those of normal volunteers (p < 0.001). Patients with higher serum HSP90 alpha levels significantly exhibited elevated levels of integrin alpha(V) mRNA in tumor tissues as compared with adjacent non-tumor tissues (p < 0.001). Furthermore, tumor integrin alpha(V) overexpression was significantly correlated with TNM (Tumor, Node, Metastasis) staging (p = 0.001).
    日期: 2010-08
    關聯: Journal of Biological Chemistry. 2010 Aug;285(33):25458-25466.
    Link to: http://dx.doi.org/10.1074/jbc.M110.139345
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000280682400039
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77955477214
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