title: P21-activated kinase 4 overexpression in metastatic gastric cancer patients.
abstract: BACKGROUND
  P21-activated kinase 4 (PAK), a subfamily of serine/threonine kinases originally known as a regulator of cytoskeletal dynamics and cell motility, has recently been revealed to play a key role in oncogenic signaling pathways. We studied the frequency and clinical features of PAK4-overexpressed metastatic gastric cancer.
  
  
  METHODS
  PAK4 overexpression was screened by Western blot in 18 human gastric cancer cell lines. Immunohistochemical staining of PAK4 protein was performed in tumor specimens of 49 metastatic gastric cancer patients who received palliative capecitabine/cisplatin as first-line treatment.
  
  
  RESULTS
  PAK4 protein overexpression was detected strongly in five gastric cell lines (AGS, MGK-28, MKN-74, SNU-216, SNU-601) and weakly in four cell lines (KATOIII, MKN-1, SNU-620, and SNU-719). PAK4 knockdown by small interfering RNA induced apoptosis in PAK4-overexpressed AGS gastric cancer cells. Immunohistochemical staining revealed PAK4 overexpressions in 4 (8.1%) of 49 metastatic gastric cancer specimens. None of the four patients with PAK4(+) responded to capecitabine/cisplatin chemotherapy, and PAK4(+) gastric cancer patients had a trend of poorer survival compared with PAK(-)(P = .876).
  
  
  CONCLUSIONS
  We demonstrated PAK4 overexpression in a subset of gastric cancer patients, implicating a role in gastric cancer tumorigenesis. Its prognostic significance and efficacy as a drug target should be further studied.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Ahn
authors.forename: Jiryeon
authors.initials: J
authors.lastname: Jang
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Park
authors.initials: P
authors.lastname: Se Hoon
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang