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Akt1 通过调节整合素 β₃的亲和力来介导前列腺癌细胞的微侵袭和对转移刺激物的趋化作用。

Akt1 mediates prostate cancer cell microinvasion and chemotaxis to metastatic stimuli via integrin β₃ affinity modulation.

机构信息

Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Georgia Health Sciences University, HM1200, Augusta, GA 30912, USA.

出版信息

Br J Cancer. 2012 Aug 7;107(4):713-23. doi: 10.1038/bjc.2012.295. Epub 2012 Jul 5.

DOI:10.1038/bjc.2012.295
PMID:22767145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3419951/
Abstract

BACKGROUND

Activation of Akt and increased expression of integrin β(3) are the two most important changes that have been linked to the attainment of metastatic potential by prostate cancer cells. However, a direct link between Akt activity and inside-out activation of integrin β(3) in mediating prostate cancer cell metastatic properties is not established.

METHODS

Using functional and biochemical approaches, we examined the role of Akt1 in the affinity modulation of integrin β(3) in prostate cancer cells.

RESULTS

Although expression of murine TRAMP and human PC3 cells with constitutively active Akt1 (CA-Akt1) enhanced their affinity for integrin α(v)β(3) specific ligands and motility on various extracellular matrix proteins, the reverse was observed with the expression of dominant-negative Akt1 (DN-Akt1). Although enhanced motility and transendothelial migration of CA-Akt1-expressing cells were blunted by co-expression with DN-integrin β(3) or upon pre-treatment with integrin β(3)-blocking antibodies (LM 609), impaired motility and transendothelial migration of DN-Akt1-expressing cells were rescued by pre-treatment of prostate cancer cells with integrin β(3)-activating antibodies, AP7.4.

CONCLUSION

Our data is the first to demonstrate a link between Akt1 activity and affinity modulation of integrin β(3) in the regulation of prostate cancer cell motility, transendothelial migration and chemotaxis to metastatic stimuli.

摘要

背景

Akt 的激活和整合素 β(3)表达的增加是与前列腺癌细胞获得转移潜能相关的两个最重要的变化。然而， Akt 活性与整合素 β(3)的内在激活在介导前列腺癌细胞转移特性方面的直接联系尚未建立。

方法

我们使用功能和生化方法研究了 Akt1 在调节前列腺癌细胞整合素 β(3)亲和力中的作用。

结果

尽管表达组成性激活 Akt1 (CA-Akt1) 的鼠 TRAMP 和人 PC3 细胞增强了它们与整合素 α(v)β(3)特异性配体的亲和力，以及在各种细胞外基质蛋白上的迁移能力，但表达显性失活 Akt1 (DN-Akt1) 则相反。尽管 CA-Akt1 表达细胞的增强迁移和跨内皮迁移被与 DN-整合素 β(3)共表达或用整合素 β(3)阻断抗体 (LM 609) 预处理所减弱，但 DN-Akt1 表达细胞的迁移能力受损和跨内皮迁移可以通过用整合素 β(3)激活抗体 AP7.4 预处理前列腺癌细胞而得到挽救。

结论

我们的数据首次证明了 Akt1 活性与整合素 β(3)亲和力调节在调节前列腺癌细胞迁移、跨内皮迁移和向转移性刺激物趋化中的联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/982c20a896a7/bjc2012295f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/c84914fc8610/bjc2012295f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/6e7b6dfa3624/bjc2012295f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/4bfe55ee89dd/bjc2012295f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/eafaffdb80b4/bjc2012295f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/1abc7cd7329f/bjc2012295f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/44c715a23b27/bjc2012295f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/da454a2b23f6/bjc2012295f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/aa92b2b5946e/bjc2012295f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/dfd7356af6ec/bjc2012295f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/982c20a896a7/bjc2012295f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/c84914fc8610/bjc2012295f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/6e7b6dfa3624/bjc2012295f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/4bfe55ee89dd/bjc2012295f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/eafaffdb80b4/bjc2012295f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/1abc7cd7329f/bjc2012295f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/44c715a23b27/bjc2012295f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/da454a2b23f6/bjc2012295f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/aa92b2b5946e/bjc2012295f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/dfd7356af6ec/bjc2012295f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c72/3419951/982c20a896a7/bjc2012295f10.jpg

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