PAK4 Phosphorylates p53 at Serine 215 to Promote Liver Cancer Metastasis
PAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion, and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A no...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2016-10, Vol.76 (19), p.5732-5742 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | Xu, Hai-Tao Lai, Wai-Lung Liu, Heong-Fai Wong, Leo Lap-Yan Ng, Irene Oi-Lin Ching, Yick Pang |
| description | PAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion, and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of our studies. By stably overexpressing or silencing PAK4 in HCC cells, we showed that it was critical for their migration. Mechanistic investigations in this setting revealed that PAK4 directly phosphorylated p53 at S215, which not only attenuated transcriptional transactivation activity but also inhibited p53-mediated suppression of HCC cell invasion. Taken together, our results showed how PAK4 overexpression in HCC promotes metastatic invasion by regulating p53 phosphorylation. Cancer Res; 76(19); 5732-42. ©2016 AACR. |
| doi_str_mv | 10.1158/0008-5472.can-15-3373 |
| format | Article |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Cell Line, Tumor Cell Movement DNA - metabolism Humans Liver Neoplasms - pathology Neoplasm Metastasis p21-Activated Kinases - analysis p21-Activated Kinases - physiology Phosphorylation Serine - metabolism Tumor Suppressor Protein p53 - metabolism |
| title | PAK4 Phosphorylates p53 at Serine 215 to Promote Liver Cancer Metastasis |
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