Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration
1
Department of Anatomy, Guangdong Provincial Key Laboratory of Tissue Construction and Detection, Southern Medical University, Guangzhou 510515, China
2
Department of Histology and Embryology, Southern Medical University, Guangzhou 510515, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1437; https://doi.org/10.3390/ijms19051437
Received: 27 February 2018 / Revised: 4 May 2018 / Accepted: 5 May 2018 / Published: 11 May 2018
(This article belongs to the Section Biochemistry)
Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR) positively correlates with TNM (tumor-node-metastasis) stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression. In addition, molecules downstream of Rho A, including ROCK1, LIMK2, and Cofilin, are activated by EGF in MG63 cells, leading to actin stress fiber formation and cell migration. Moreover, inhibition of ROCK1, LIMK2, or Cofilin in MG63 cells using known inhibitors or short hairpin RNA (shRNA) prevents actin stress fiber formation and cell migration. Thus, we conclude that Rho A/ROCK1/LIMK2/Cofilin signaling mediates actin microfilament formation in MG63 cells upon EGFR activation. This novel pathway provides a promising target for preventing osteosarcoma progression and for treating this cancer.
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Keywords:
osteosarcoma; migration; stress fiber; Rho A
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MDPI and ACS Style
Wang, J.; Zhang, L.; Qu, R.; Zhang, L.; Huang, W. Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration. Int. J. Mol. Sci. 2018, 19, 1437.
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