Chuanyu Sun, Yuqing Zhu, Chong Xu, Guowei Xia, Xiaojun Zhao
1 Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
2 Department of Immunology, Shanghai Centre for Clinical Laboratory, Shanghai, China.
Tumour Biol. 2017 Apr;39(4):1010428317694549. doi: 10.1177/1010428317694549.
Periostin (POSTN) is an extracellular matrix protein which is overexpressed in a variety of cancers and has been related to tumorigenesis of renal cell carcinoma. However, the involvement of POSTN in renal cell carcinoma migration, invasion, and their underlying mechanisms has not been established. In this study, renal cell carcinoma cell lines stably overexpressing POSTN were established using a lentiviral vector, and the effects of POSTN on renal cell carcinoma cell migration and invasion were investigated. POSTN overexpression increased the migration and invasion capabilities of renal cell carcinoma cell lines as well as activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. Integrin αβ and αβ antibodies inhibited POSTN overexpression or recombinant POSTN-induced focal adhesion kinase activation, cell migration, and invasion. Furthermore, lentivirus-mediated focal adhesion kinase knockdown and c-Jun N-terminal kinase inhibitor reduced POSTN-enhanced phosphorylation of c-Jun N-terminal kinase, matrix metalloproteinase-9 and matrix metalloproteinase-2 expressions, cell migration, and invasion. Our research thus indicates that POSTN promotes renal cell carcinoma cell migration and invasion through interaction with integrins αβ and αβ and subsequent activation of the focal adhesion kinase/c-Jun N-terminal kinase pathway. These results suggest that POSTN plays a critical role in renal cell carcinoma metastasis and may represent a potential target for novel therapeutic approaches against renal cell carcinoma.
骨膜蛋白（POSTN）是一种细胞外基质蛋白，在多种癌症中过度表达，且与肾细胞癌的肿瘤发生有关。然而，POSTN在肾细胞癌迁移、侵袭及其潜在机制中的作用尚未明确。在本研究中，使用慢病毒载体建立了稳定过表达POSTN的肾癌细胞系，并研究了POSTN对肾癌细胞迁移和侵袭的影响。POSTN过表达增加了肾癌细胞系的迁移和侵袭能力以及基质金属蛋白酶-2和基质金属蛋白酶-9的活性。整合素αβ和αβ抗体抑制了POSTN过表达或重组POSTN诱导的粘着斑激酶激活、细胞迁移和侵袭。此外，慢病毒介导的粘着斑激酶敲低和c-Jun氨基末端激酶抑制剂降低了POSTN增强的c-Jun氨基末端激酶磷酸化、基质金属蛋白酶-9和基质金属蛋白酶-2表达、细胞迁移和侵袭。因此，我们的研究表明，POSTN通过与整合素αβ和αβ相互作用并随后激活粘着斑激酶/c-Jun氨基末端激酶途径促进肾癌细胞迁移和侵袭。这些结果表明，POSTN在肾细胞癌转移中起关键作用，可能代表针对肾细胞癌的新型治疗方法的潜在靶点。
