Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma

  • Authors:
    • Dingyuan Luo
    • Haibo Chen
    • Xiaojuan Li
    • Penghui Lu
    • Miaoyun Long
    • Xinzhi Peng
    • Shaojian Lin
    • Langping Tan
    • Yue Zhu
    • Nengtai Ouyang
    • Honghao Li
  • View Affiliations

  • Published online on: August 23, 2017     https://doi.org/10.3892/ijo.2017.4100
  • Pages: 1209-1218
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Abstract

Rho-associated protein kinase 1 (ROCK1), a serine/threonine kinase, has previously been shown to be over-expressed in various types of human malignant tumors and to play an important role in cancer development and progression. Although ROCK1 has gained growing prominence as an important protein kinase in cancer biology, its potential as a predictive biomarker and a therapeutic target in papillary thyroid carcinoma (PTC) remains unknown. In the present study, ROCK1 expression was examined in 356 formalin-fixed, paraffin-embedded papillary thyroid carcinoma tissues using immunohistochemistry, and its clinical implications and prognostic significance were analyzed. Our results showed that ROCK1 expression was significantly increased in PTC compared with normal tissues, and was significantly associated with tumor size, lymphatic metastasis, distant organ metastasis, extrathyroid invasion, vascular invasion and tumor, node and metastasis (TNM) stage. Patients with strong ROCK1 expression had lower overall survival, disease-free survival, lymph node recurrence-free survival and distant recurrence-free survival rates than those with weak expression. Furthermore, overexpression of ROCK1 in papillary thyroid carcinoma cells was found to increase their invasiveness. Silencing ROCK1 by siRNA, however, caused an inhibition of cell invasion. Knockdown of ROCK1 decreased the volume and weight of the xenograft tumors, while overexpression of ROCK1 showed a proliferative tendency with significantly greater tumor volume and weight in vivo. Moreover, the upregulation of ROCK1 increased the expression of MMP-9, and levels of MMP-9 positively correlated with the ROCK1 levels in PTC tissues, implicating that MMP-9 may be involved in the mechanism of ROCK1 in the development and progression of PTC. These data suggest that ROCK1 might be a potential prognostic marker and therapeutic target for the treatment of PTC.
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October-2017
Volume 51 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Luo D, Chen H, Li X, Lu P, Long M, Peng X, Lin S, Tan L, Zhu Y, Ouyang N, Ouyang N, et al: Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma. Int J Oncol 51: 1209-1218, 2017
APA
Luo, D., Chen, H., Li, X., Lu, P., Long, M., Peng, X. ... Li, H. (2017). Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma. International Journal of Oncology, 51, 1209-1218. https://doi.org/10.3892/ijo.2017.4100
MLA
Luo, D., Chen, H., Li, X., Lu, P., Long, M., Peng, X., Lin, S., Tan, L., Zhu, Y., Ouyang, N., Li, H."Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma". International Journal of Oncology 51.4 (2017): 1209-1218.
Chicago
Luo, D., Chen, H., Li, X., Lu, P., Long, M., Peng, X., Lin, S., Tan, L., Zhu, Y., Ouyang, N., Li, H."Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma". International Journal of Oncology 51, no. 4 (2017): 1209-1218. https://doi.org/10.3892/ijo.2017.4100