Fibrillin-1, induced by Aurora-A but inhibited by BRCA2, promotes ovarian cancer metastasis.
Fibrillin-1, induced by Aurora-A but inhibited by BRCA2, promotes ovarian cancer metastasis.
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Fibrillin-1 由 Aurora-A 诱导但受 BRCA2 抑制，可促进卵巢癌转移。
DOI：
10.18632/oncotarget.3118
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发表时间：
2015-03-30
期刊：
影响因子：
--
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Wang Z;Liu Y;Lu L;Yang L;Yin S;Wang Y;Qi Z;Meng J;Zang R;Yang G
Aurora-A（Aur A）引起原发性肿瘤的发生，而BRCA 2抑制原发性肿瘤的发生，Aur A和BRCA 2在癌症转移中的作用尚不清楚。在这里，我们发现转移促进标志物SLUG，FBN 1和MMP 2，9，13被Aur A或BRCA 2刺激或抑制，但转移抑制因子E-钙粘蛋白，β-连环蛋白和p53被Aur A或BRCA 2抑制或促进，导致增强或减少细胞迁移和侵袭。进一步的研究表明，FBN 1抑制E-钙粘蛋白和β-连环蛋白，但刺激MMP 2，9，13。SLUG的耗尽废除了FBN 1和MMP 9，但增加了E-钙粘蛋白，而p53降低了SLUG和FBN 1。动物实验表明，FBN 1促进卵巢肿瘤发生和转移。临床上，BRCA 2或Aur A在卵巢癌组织中的过表达预示着良好或不良的总体和无病生存。SLUG或FBN 1的高表达表明总体生存率差，而FBN 1而非SLUG的高表达预示无病生存率差。FBN 1位于Aur A和BRCA 2的下游，通过p53和SLUG相关信号通路促进卵巢癌的转移，可能对卵巢癌的诊断和治疗有一定的参考价值。
While Aurora-A (Aur A) provokes, BRCA2 restrains primary tumorigenesis, the roles of Aur A and BRCA2 in cancer metastasis remains unclear. Here, we show that the metastatic promoting markers SLUG, FBN1, and MMP2, 9, 13 are either stimulated or suppressed by Aur A or BRCA2, but the metastatic suppressors E-cadherin, β-catenin, and p53 are either inhibited or promoted by Aur A or BRCA2, leading to enhanced or reduced cell migration and invasion. Further study suggests that FBN1 inhibits E-cadherin and β-catenin, but stimulates MMP2, 9, 13. Depletion of SLUG abrogates FBN1 and MMP9, but increases E-cadherin, while p53 decreases both SLUG and FBN1. Animal assays demonstrate that FBN1 promotes both ovarian tumorigenesis and metastasis. Clinically, overexpression of BRCA2 or Aur A in ovarian cancer tissues predicts good or poor overall and disease free survivals. High expression of SLUG or FBN1 indicates poor overall survivals, whereas high expression of FBN1 but not of SLUG predicts poor disease free survival. No significant associations between p53 expression and patient survivals were found. Overall, FBN1, acts at the downstream of Aur A and BRCA2, promotes ovarian cancer metastasis through the p53 and SLUG-associated signaling, which may be useful for ovarian cancer diagnosis and treatment.
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影响因子：
3.8
作者：
Haslehurst AM;Koti M;Dharsee M;Nuin P;Evans K;Geraci J;Childs T;Chen J;Li J;Weberpals J;Davey S;Squire J;Park PC;Feilotter H
通讯作者：
Feilotter H
影响因子：
8.8
作者：
Goos, J. A. C. M.;Coupe, V. M. H.;Diosdado, B.;Diemen, P. M. Delis-Van;Karga, C.;Belien, J. A. M.;Carvalho, B.;van den Tol, M. P.;Verheul, H. M. W.;Geldof, A. A.;Meijer, G. A.;Hoekstra, O. S.;Fijneman, R. J. A.
通讯作者：
Fijneman, R. J. A.
影响因子：
4.7
作者：
Lassus, Heini;Staff, Synnove;Butzow, Ralf
通讯作者：
Butzow, Ralf
影响因子：
2.5
作者：
GOLDSTEIN, C;LIAW, P;SIRACUSA, LD
通讯作者：
SIRACUSA, LD
影响因子：
4.8
作者：
Li, QY;Kaneko, S;Cheng, JQ
通讯作者：
Cheng, JQ