PAK5 overexpression is associated with lung metastasis in osteosarcoma

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.

Dark kinase annotation, mining and visualization using the Protein Kinase Ontology

“…With the addition of the new GeneExpression class in ProKinO and the RDF triples connecting gene expression to the Sample and Protein classes (GeneExpression:InSample: Sample; GeneExpression:hasProtein: Protein), one can formulate queries requesting for PAK5 expression in different samples. Rank ordering the samples based on PAK5 expression (Query 33) reveals cancer types such as adenocarcinoma (Zscore: 4701.5) and hepatocellular carcinoma (Zscore: 2038.2) that have previously been associated with abnormal PAK5 expression (63)(64)(65)(66). However, the role of PAK5 in other cancer types such as acute myeloid leukemia (Zscore: 136.4) is relatively understudied (67).…”

Down-Regulated microRNA-34a Expression as a Prognostic Marker for Poor Osteosarcoma in Mice: A Systematic Review and Meta-Analysis

“…Osteosarcoma, as the most common primary malignant bone tumor, has high mortality rate and metastasis rate. With the progress of neoadjuvant chemotherapy, the 5-year survival rate in patients without metastasis is less than 70 percent 18 , while the survival rate of patients with metastasis or relapse is still lower than 20% 3 . Therefore, it is essential to develop new therapeutic strategies for osteosarcoma.…”

“…Despite the fact that there are aggressive tumor resection, combinatorial chemotherapy and radiotherapy treatments, the five-year survival rate of osteosarcoma patient without metastasis is only about sixty percent to seventy percent 1 , 2 . The survival rate of patients with metastasis or relapse is still below 20% 3 .Therefore, it is essential to develop new therapeutic approaches for osteosarcoma treatment.…”

PAK6 promotes cervical cancer progression through activation of the Wnt/β‑catenin signaling pathway

“…Previous studies have revealed that the PAK family was involved in numerous cellular functions, such as cell motility, cell survival and gene regulation ( 6 , 7 ). The overexpression or amplification of PAKs has been detected in several types of human tumor, including breast cancer, neurofibromatosis, colon cancer and lung cancer ( 8 , 9 ), and it has been reported to be involved in several cancer signaling pathways, including the NF-κB, Ras, AKT, Raf and p53 pathways ( 10 – 13 ). Thus, the different biological roles of PAKs have positioned them as attractive cancer therapeutic targets.…”