Gelsolin promotes cell growth and invasion through the upregulation of p-AKT and p-P38 pathway in osteosarcoma

Xiaojun Ma; Wei Sun; Jiakang Shen; Yingqi Hua; Fei Yin; Mengxiong Sun; Zhengdong Cai

doi:10.1007/s13277-015-4565-x

Gelsolin promotes cell growth and invasion through the upregulation of p-AKT and p-P38 pathway in osteosarcoma

Tumour Biol. 2016 Jun;37(6):7165-74. doi: 10.1007/s13277-015-4565-x. Epub 2015 Dec 12.

Authors

Xiaojun Ma¹, Wei Sun¹, Jiakang Shen¹, Yingqi Hua¹, Fei Yin¹, Mengxiong Sun¹, Zhengdong Cai²

Affiliations

¹ Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
² Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China. czd856@vip.163.com.

PMID: 26662962
DOI: 10.1007/s13277-015-4565-x

Abstract

The gelsolin (GSN) has been involved in the regulation of tumor formation and development, but the biological role of GSN in the pathogenesis of osteosarcoma (OS) has not been well characterized. In this study, we show that high expression of GSN was observed in OS tissues and correlated with tumor size, advanced Enneking stage, and poor patient prognosis. Knockdown of GSN significantly inhibited cell proliferation and invasiveness in the OS cell lines. Furthermore, stable overexpression of GSN in OS cells resulted in a significant increase in cell growth and motility with the downregulation of p-AKT and p-P38 pathway. Finally, overexpression of GSN promoted growth of OS tumors in SCID mice. Taken together, these results provided the first evidence that GSN might contribute to OS cancer development and could be an attractive therapeutic target for patients with OS.

Keywords: GSN; Invasion; Osteosarcoma; Prognosis; Proliferation.

MeSH terms

Adolescent
Animals
Apoptosis / drug effects
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Blotting, Western
Bone Neoplasms / drug therapy
Bone Neoplasms / metabolism
Bone Neoplasms / pathology
Cell Movement / drug effects*
Cell Proliferation / drug effects*
Female
Follow-Up Studies
Gelsolin / pharmacology*
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Immunoenzyme Techniques
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Staging
Osteosarcoma / drug therapy
Osteosarcoma / metabolism
Osteosarcoma / pathology*
Prognosis
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Biomarkers, Tumor
Gelsolin
RNA, Messenger
Proto-Oncogene Proteins c-akt
p38 Mitogen-Activated Protein Kinases