Effects of PAK4/LIMK1/Cofilin-1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells.

Abstract

PURPOSE:

To explore the effects of PAK4/LIMK1/Cofilin-1 signaling pathway on the proliferation, invasion, and migration of human osteosarcoma cells.

METHODS:

The expression of PAK4/LIMK1/Cofilin-1 was detected by immunohistochemistry in osteosarcoma tissues. The osteosarcoma cell line MG63 was transfected and divided into Mock, Control siRNA, si-PAK4, LIMK1, and si-PAK4+LIMK1 groups. Then, the cellular biological features of MG63 cells were detected by CCK-8, wound-healing, Transwell, and flow cytometry methods. The relationship of PAK4 and LIMK1 was performed by co-immunoprecipitation test, and the protein expression of PAK4/LIMK1/Cofilin-1 was determined by Western blotting. Finally, the effect of PAK4 on the growth of osteosarcoma was verified by subcutaneous transplantation model of osteosarcoma in nude mice.

RESULTS:

The expression of PAK4/LIMK1/Cofilin-1 in both osteosarcoma tissues and cells was up-regulated. Positive PAK4, LIMK1, and Cofilin-1 expressions in osteosarcoma were associated with the clinical stage, distant metastasis, and tumor grade. The MG63 cell viability, migration, and invasion, as well as the expression of PAK4, p-LIMK/LIMK, and p-Cofilin-1/Cofilin-1, were restrained by the knock down of PAK4 while it promoted apoptosis. PAK4 silencing also suppressed the growth of subcutaneous transplanted tumor in nude mice. Co-immunocoprecipitation showed that LIMK and PAK4 protein can form complex in osteosarcoma cells. Besides, LIMK1 overexpression reversed the inhibition effect of PAK4 siRNA on the growth of osteosarcoma cells.

CONCLUSION:

The expression of PAK4/LIMK1/Cofilin-1 pathway in osteosarcoma tissues was up-regulated. Thus, PAK4 inhibition may restrict the osteosarcoma cell proliferation, invasion, and migration but promote its apoptosis via decreasing the activity of LIMK1/Cofilin-1 pathway.

• Authors: Zhi-Feng Li, Yin-Di Yao, Yin-Yin Zhao, Yan Liu, Zhen-Hua Liu, Pei Hu, Zhuo-Ran Zhu
• Journal: Journal of clinical laboratory analysis (J Clin Lab Anal) Vol. 34 Issue 9 Pg. e23362 (Sep 2020) ISSN: 1098-2825 [Electronic] United States
• PMID: 32463132 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.

Chemical References

• Biomarkers, Tumor
• Cofilin 1
• PAK4 protein, human
• LIMK1 protein, human
• Lim Kinases
• p21-Activated Kinases

Topics

• Adult
• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Bone Neoplasms (genetics, metabolism, pathology)
• Cell Movement
• Cell Proliferation
• Cofilin 1 (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lim Kinases (genetics, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Osteosarcoma (genetics, metabolism, pathology)
• Prognosis
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Young Adult
• p21-Activated Kinases (genetics, metabolism)