Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer.
Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer.
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DOI：
10.18632/oncotarget.19475
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Kuo PL
中科院分区：
文献类型：
--
作者：
Hung JY;Yen MC;Jian SF;Wu CY;Chang WA;Liu KT;Hsu YL;Chong IW;Kuo PL
细胞外基质是生理微环境的组成部分，也是细胞过程如迁移和增殖的调节剂。分泌的酸性蛋白和富含半胱氨酸（骨粘连蛋白）是一种细胞外基质相关的糖蛋白，参与调节几种类型的癌症中的细胞增殖和细胞迁移。然而，在肺癌中的作用是自相矛盾的，并没有众所周知的调控机制的细节。在这项研究中，我们研究了新的SPARC介导的信号通路。在两种非小细胞肺癌细胞系CL1 - 5和H1299中，顺铂治疗增加了细胞增殖、迁移和间充质表型。我们发现这些表型不受粘着斑激酶和Src激酶的调节，而是由无赖氨酸（K）激酶1（WNK 1）介导的。抑制WNK 1的表达降低了SPARC诱导的N-钙粘蛋白和平滑肌肌动蛋白的表达。此外，Snail作为调节上皮-间质转化的重要转录因子，也参与了EST-WNK 1通路。在鼠肿瘤模型中，与对照小鼠相比，顺铂治疗显著诱导肺肿瘤结节中Akt和WNK 1的磷酸化。总之，这些数据表明，WNK 1是一个新的分子在SPARC介导的非小细胞肺癌间充质信号通路。
The extracellular matrix is a component of physiological microenvironment and a regulator of cellular processes such as migration and proliferation. Secreted Protein Acidic and Rich in Cysteine (SPARC/osteonectin) is an extracellular matrix-associated glycoprotein involved in the regulation of cell proliferation and cell migration in several types of cancers. However, the role of SPARC in lung cancer is paradoxical and details of the regulatory mechanism are not well-known. In this study, we investigated novel SPARC-mediated signaling pathways. Treatment of SPARC increased cell proliferation, migration, and mesenchymal phenotype in two non-small cell lung cancer cell lines, CL1-5 and H1299. We found that these phenotypes were not regulated by focal adhesion kinase and Src kinase, but were mediated by with no lysine (K) kinase 1 (WNK1). Suppression of WNK1 expression decreased the expression of SPARC-induced N-cadherin and smooth muscle actin. Moreover, Snail, an important transcription factor for regulating epithelial–mesenchymal transition, is also involved in SPARC/WNK1 pathway. In a murine tumor model, SPARC treatment significantly induced phosphorylation of Akt and WNK1 in lung tumor nodules when compared to control mice. In conclusion, these data suggest that WNK1 is a novel molecule in SPARC-mediated mesenchymal signaling pathway in non-small cell lung cancer.
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影响因子：
--
作者：
Hsu YL;Hung JY;Chiang SY;Jian SF;Wu CY;Lin YS;Tsai YM;Chou SH;Tsai MJ;Kuo PL
通讯作者：
Kuo PL
影响因子：
--
作者：
Hsu YL;Hung JY;Liang YY;Lin YS;Tsai MJ;Chou SH;Lu CY;Kuo PL
通讯作者：
Kuo PL
影响因子：
8
作者：
Navab R;Strumpf D;To C;Pasko E;Kim KS;Park CJ;Hai J;Liu J;Jonkman J;Barczyk M;Bandarchi B;Wang YH;Venkat K;Ibrahimov E;Pham NA;Ng C;Radulovich N;Zhu CQ;Pintilie M;Wang D;Lu A;Jurisica I;Walker GC;Gullberg D;Tsao MS
通讯作者：
Tsao MS
影响因子：
4.2
作者：
Da, Chunli;Liu, Yuting;Wang, Ruozheng
通讯作者：
Wang, Ruozheng
影响因子：
4.8
作者：
Barker, TH;Baneyx, G;Sage, EH
通讯作者：
Sage, EH