PAK5 overexpression is associated with lung metastasis in osteosarcoma

Han,Kun; Zhou,Yan; Tseng,Kuo‑Fu; Hu,Haiyan; Li,Kunpeng; Wang,Yaling; Gan,Zhihua; Lin,Shuchen; Sun,Yongning; Min,Daliu

doi:10.3892/ol.2017.7545

PAK5 overexpression is associated with lung metastasis in osteosarcoma

Authors:
- Kun Han
- Yan Zhou
- Kuo‑Fu Tseng
- Haiyan Hu
- Kunpeng Li
- Yaling Wang
- Zhihua Gan
- Shuchen Lin
- Yongning Sun
- Daliu Min
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Affiliations: Oncology Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China, Biophysics Department of Oregon State University, Corvallis, OR 97330, USA, School of Life Sciences, Sun Yat‑Sen University, Guangzhou, Guangdong 510275, P.R. China
Published online on: December 7, 2017 https://doi.org/10.3892/ol.2017.7545
Pages: 2202-2210
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

p21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases, which are associated with cytoskeletal organization, cellular morphogenesis, migration and survival. PAKs are overactive in a number of tumor tissues and have attracted attention as a potential target for cancer therapy. In the present study, PAK5 levels were analyzed in primary osteosarcoma (OS) samples (n=65) using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry (IHC) methods. In the primary OS tissue, increased PAK5 expression (IHC score >2, n=37) was associated with significantly decreased overall survival (P=0.036) compared with decreased PAK5 expression (IHC score ≤2, n=28). PAK5 expression was identified to be significantly associated with metastasis (P=0.010). The lung is the most common metastasis site for OS. In addition, the level of PAK5 in lung metastasis tissue (n=13) was detected using RT‑qPCR and IHC methods. PAK5 expression was increased in lung metastasis tissue compared with in primary OS samples. PAK5 was silenced using short hairpin RNA in OS cell lines. Wound healing, migration and nude mice model assay results consistently demonstrated that PAK5 knockdown was able to significantly inhibit OS migration. In PAK5‑knockdown cells, the alteration in the expression of a number of metastasis‑associated factors, including epithelial cadherin, vimentin, fibronectin and matrix metalloproteinase 2 (MMP2), was analyzed. Only MMP2 expression was decreased significantly (P<0.05). The expression level of MMP2 was analyzed in primary OS tissue and lung metastasis tissue using RT‑qPCR and IHC methods. Expression of MMP2 was identified to be associated with expression of PAK5. The results of the present study suggest that PAK5 promotes OS cell migration and that PAK5 expression may be used to predict lung metastasis.

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