American Association for Cancer Research
Browse
00085472can104046-sup-sfig_2.pdf (60.34 kB)

Supplementary Figure 2 from Overexpression of a Novel Activator of PAK4, the CDK5 Kinase–Associated Protein CDK5RAP3, Promotes Hepatocellular Carcinoma Metastasis

Download (60.34 kB)
journal contribution
posted on 2023-03-30, 20:48 authored by Grace Wing-Yan Mak, Mandy Man-Lok Chan, Veronica Yee-Law Leong, Joyce Man-Fong Lee, Tai-On Yau, Irene Oi-Lin Ng, Yick-Pang Ching
Supplementary Figure 2 from Overexpression of a Novel Activator of PAK4, the CDK5 Kinase–Associated Protein CDK5RAP3, Promotes Hepatocellular Carcinoma Metastasis

History

ARTICLE ABSTRACT

The CDK5 kinase regulatory subunit-associated protein 3 (CDK5RAP3 or C53/LZAP) regulates apoptosis induced by genotoxic stress. Although CDK5RAP3 has been implicated in cancer progression, its exact role in carcinogenesis is not well established. In this article, we report that CDK5RAP3 has an important prometastatic function in hepatocarcinogenesis. An examination of human hepatocellular carcinoma (HCC) samples revealed at least twofold overexpression of CDK5RAP3 transcripts in 58% (39/67) of HCC specimens when compared with corresponding nontumorous livers. CDK5RAP3 overexpression was associated with more aggressive biological behavior. In HCC cell lines, stable overexpression of CDK5RAP3 promoted, and small interfering RNA–mediated knockdown inhibited, tumorigenic activity and metastatic potential. We found that overexpression of CDK5RAP3 and p21-activated protein kinase 4 (PAK4) correlated in human HCCs, and that CDK5RAP3 was a novel binding partner of PAK4, and this binding enhanced PAK4 activity. siRNA-mediated knockdown of PAK4 in CDK5RAP3-expressing HCC cells reversed the enhanced cell invasiveness mediated by CDK5RAP3 overexpression, implying that PAK4 is essential for CDK5RAP3 function. Taken together, our findings reveal that CDK5RAP3 is widely overexpressed in HCC and that overexpression of CDK5RAP3 promotes HCC metastasis through PAK4 activation. Cancer Res; 71(8); 2949–58. ©2011 AACR.

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC