TNFα-mediated loss of β-catenin/E-cadherin association and subsequent increase in cell migration is partially restored by NKX3.1 expression in prostate cells.
TNFα-mediated loss of β-catenin/E-cadherin association and subsequent increase in cell migration is partially restored by NKX3.1 expression in prostate cells.
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DOI：
10.1371/journal.pone.0109868
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Korkmaz KS
中科院分区：
文献类型：
--
作者：
Debelec-Butuner B;Alapinar C;Ertunc N;Gonen-Korkmaz C;Yörükoğlu K;Korkmaz KS
炎症诱导的致癌作用与多种肿瘤细胞的增殖以及迁移/侵袭增加有关。在本研究中，我们检测了前列腺癌细胞在肿瘤坏死因子α（TNFα）暴露下β-连环蛋白信号通路的改变，以及其与肿瘤抑制因子NKX3.1功能丧失的关系。我们利用体外前列腺炎症模型证明，在Akt（S473）和GSK3β（S9）磷酸化增加后，β -连环蛋白的亚细胞定位发生改变。一致地，我们观察到β -连环蛋白反式激活的后续增加增强了c - myc、细胞周期蛋白D1和MMP2的表达。因此，还观察到在急性细胞因子暴露期间，质膜上的β -连环蛋白 - E -钙黏蛋白结合被破坏。此外，在实时迁移实验中证明，破坏细胞 - 细胞相互作用导致LNCaP细胞迁移增加。然而，发现在炎症中因促炎细胞因子暴露而降解的NKX3.1的异位表达通过抑制Akt（S473）磷酸化诱导β -连环蛋白的降解，因此，部分挽救了细胞因子暴露时LNCaP细胞中被破坏的β -连环蛋白 - E -钙黏蛋白相互作用以及细胞迁移。因为在伴有前列腺炎症萎缩（PIA）、高级别前列腺上皮内瘤变（H - PIN）以及与NKX3.1表达缺失相关的癌性病变的人前列腺组织中，观察到β -连环蛋白在细胞膜上的定位被破坏以及Akt（S308）起始磷酸化增加。因此，数据表明β -连环蛋白信号通路；进而其亚细胞定位在炎症中失调，与前列腺萎缩和PIN病理相关。
Inflammation-induced carcinogenesis is associated with increased proliferation and migration/invasion of various types of tumor cells. In this study, altered β-catenin signaling upon TNFα exposure, and relation to loss of function of the tumor suppressor NKX3.1 was examined in prostate cancer cells. We used an in vitro prostate inflammation model to demonstrate altered sub-cellular localization of β-catenin following increased phosphorylation of Akt(S473) and GSK3β(S9). Consistently, we observed that subsequent increase in β-catenin transactivation enhanced c-myc, cyclin D1 and MMP2 expressions. Consequently, it was also observed that the β-catenin-E-cadherin association at the plasma membrane was disrupted during acute cytokine exposure. Additionally, it was demonstrated that disrupting cell-cell interactions led to increased migration of LNCaP cells in real-time migration assay. Nevertheless, ectopic expression of NKX3.1, which is degraded upon proinflammatory cytokine exposure in inflammation, was found to induce the degradation of β-catenin by inhibiting Akt(S473) phosphorylation, therefore, partially rescued the disrupted β-catenin-E-cadherin interaction as well as the cell migration in LNCaP cells upon cytokine exposure. As, the disrupted localization of β-catenin at the cell membrane as well as increased Akt(S308) priming phosphorylation was observed in human prostate tissues with prostatic inflammatory atrophy (PIA), high-grade prostatic intraepithelial neoplasia (H-PIN) and carcinoma lesions correlated with loss of NKX3.1 expression. Thus, the data indicate that the β-catenin signaling; consequently sub-cellular localization is deregulated in inflammation, associates with prostatic atrophy and PIN pathology.
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DOI：
10.1083/jcb.153.5.1049
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Wong E;Gumbiner BM
通讯作者：
Gumbiner BM
影响因子：
4.4
作者：
He, WW;Sciavolino, PJ;Carter, KC
通讯作者：
Carter, KC
影响因子：
8
作者：
Desbois-Mouthon, C;Cadoret, A;Capeau, J
通讯作者：
Capeau, J
影响因子：
4.1
作者：
Hamid, Syed Muhammad;Cicek, Seher;Korkmaz, Kemal Sami
通讯作者：
Korkmaz, Kemal Sami
影响因子：
50.3
作者：
Lei, Qunying;Jiao, Jing;Wu, Hong
通讯作者：
Wu, Hong