Please use this identifier to cite or link to this item: http://dl.umsu.ac.ir/handle/10722/137198
Title: p21-activated kinase 4 regulates ovarian cancer cell proliferation, migration, and invasion and contributes to poor prognosis in patients
Authors: Siu, MKY;Ngan, HYS;Tsao, SW;Cheung, ANY;Li, Z;Chan, QKY;Strömblad, S;Chan, HY;Kong, DSH;Wong, ESY;Wong, OGW;Tam, KF;Zhang, H
subject: Prognostic marker;Therapeutic target
Year: 2010
Publisher: National Academy of Sciences. The Journal's web site is located at http://www.pnas.org
United States
Description: Ovarian cancer is a lethal gynecological malignancy, and to improve survival, it is important to identify novel prognostic and therapeutic targets. In this study, we present a role for p21-activated kinase 4 (Pak4) in ovarian cancer progression. We show a significant association between increased expression of Pak4 and its activated form, phosphorylated (p)-Pak4 Ser 474, with metastasis of ovarian cancers, shorter overall and disease-free survival, advanced stage and high-grade cancers, serous/clear cell histological subtypes, and reduced chemosensitivity. Pak4 overexpression was also observed in ovarian cancer cell lines. Pak4 and p-Pak4 expression were detected both in the nucleus and cytoplasm of ovarian cancer cells, in vitro as well as in vivo. Stable knockdown of Pak4 in ovarian cancer cell lines led to reduced cell migration, invasion, and proliferation, along with reduced c-Src, ERK1/2, and epidermal growth factor receptor (EGFR) activation and decreased matrix metalloproteinase 2 (MMP2) expression. Conversely, Pak4 overexpression promoted ovarian cancer cell migration and invasion in a c-Src, MEK-1, MMP2, and kinase-dependent-manner, and induced cell proliferation through the Pak4/c-Src/EGFR pathway that controls cyclin D1 and CDC25A expression. Stable knockdown of Pak4 also impeded tumor growth and dissemination in nude mice. This report reveals the association between Pak4 and important clinicopathologic parameters, suggesting Pak4 to be a significant prognostic marker and potential therapeutic molecular target in ovarian cancer. The implied possible cross-talk between Pak4 and EGFR suggests the potential of dual targeting of EGFR and Pak4 as a unique therapeutic approach for cancer therapy.
URI: http://www.scopus.com/mlt/select.url?eid=2-s2.0-78649880786&selection=ref&src=s&origin=recordpage
http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=107&issue=43&spage=18622&epage=18627&date=2010&atitle=p21-activated+kinase+4+regulates+ovarian+cancer+cell+proliferation,+migration,+and+invasion+and+contributes+to+poor+prognosis+in+patients
http://hub.hku.hk/handle/10722/137198
Standard no: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 43, p. 18622-18627
10.1073/pnas.0907481107
1091-6490
18627
191093
192465
WOS:000283677400072
0027-8424
43
PMC2972956
20926745
eid_2-s2.0-78649880786
18622
107
Appears in Collections:Department of Anatomy

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