Tumor Biology

, Volume 36, Issue 12, pp 9431–9436 | Cite as

Activated Pak4 expression correlates with poor prognosis in human gastric cancer patients

Research Article

Abstract

Despite considerable advances in gastrectomy and chemotherapy, the prognosis of gastric cancer (GC) has not noticeably improved due to lymph node or distant metastases. P21-activated serine/threonine kinase 4 (Pak4) plays an important role in cell morphology and cytoskeletal reorganization—both prerequisite steps for cell migration. However, it is still unclear if activated Pak4 (p-Pak4) is related to prognosis in GC patients. In our study, the level of p-Pak4 in 95 GC tissue specimens was examined by immunohistochemistry (IHC). We observed significant correlation between the level of p-Pak4 and grosstype (advanced stage GC vs. early stage GC, P = 0.04). Moreover, GC patients with higher p-Pak4 levels had a poorer prognosis than those with lower p-Pak4 levels (17 vs. 38 months, P = 0.001). Multivariate analysis showed that high phosphorylation level of Pak4, advanced stage GC, and lymph node metastasis were independent prognostic factors for GC patients (p-Pak4, P = 0.026; advanced stage GC, P = 0.030; lymph node metastasis, P = 0.016). In addition, in vitro assays indicated that knockdown of Pak4 accompanied with decreased p-Pak4, inhibited cell migration via downregulation of the traditional downstream signaling pathways of Pak4, LIMK1, and cofilin. In conclusion, this report reveals that high level of p-Pak4 correlates with poor prognosis in GC, thereby suggesting that p-Pak4 might be a potential prognostic marker for GC.

Keywords

p-Pak4 Gastric cancer Prognosis Migration 

Notes

Conflicts of interest

None

Funding sources

This work was supported by the National Science and Technology Major Project (No. 2013ZX09303002) and the National Natural Science Foundation of China (Nos. 81270036, 81472193, 81372546, 81372485).

Supplementary material

13277_2015_3368_Fig4_ESM.jpg (63 kb)
Supplementary 1

Western blot illustrating the specificity of the p-Pak4 Ser474 antibody using samples of gastric cancer. (JPEG 62 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Medical OncologyThe First Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Respiratory and Infectious disease of GeriatricsThe First Hospital of China Medical UniversityShenyangChina

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