標題: PSPC1-interchanged interactions with PTK6 and beta-catenin synergize oncogenic subcellular translocations and tumor progression
作者: Lang, Yaw-Dong
Chen, Hsin-Yi
Ho, Chun-Ming
Shih, Jou-Ho
Hsu, En-Chi
Shen, Roger
Lee, Yu-Ching
Chen, Jyun-Wei
Wu, Cheng-Yen
Yeh, Hsi-Wen
Chen, Ruey-Hwa
Jou, Yuh-Shan
生物資訊及系統生物研究所
Institude of Bioinformatics and Systems Biology
公開日期: 16-十二月-2019
摘要: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to metastasis. Paraspeckle component 1 (PSPC1) upregulation has been identified as an HCC pro-metastatic activator associated with poor patient prognosis, but with a lack of targeting strategy. Here, we report that PSPC1, a nuclear substrate of PTK6, sequesters PTK6 in the nucleus and loses its metastasis driving capability. Conversely, PSPC1 upregulation or PSPC1-Y523F mutation promotes epithelial-mesenchymal transition, stemness, and metastasis via cytoplasmic translocation of active PTK6 and nuclear translocation of p-catenin, which interacts with PSPC1 to augment Wnt3a autocrine signaling. The aberrant nucleocytoplasmic shuttling of active PTK6/beta-catenin is reversed by expressing the PSPC1 C-terminal interacting domain (PSPC1-CT131), thereby suppressing PSPC1/PTK6/beta-catenin-activated metastasis to prolong the survival of HCC orthotopic mice. Thus, PSPC1 is the contextual determinant of the oncogenic switch of PTK6/beta-catenin subcellular localizations, and PSPC1-CT131 functions as a dual inhibitor of PSPC1 and PTK6 with potential for improving cancer therapy.
URI: http://dx.doi.org/10.1038/s41467-019-13665-6
http://hdl.handle.net/11536/153379
ISSN: 2041-1723
DOI: 10.1038/s41467-019-13665-6
期刊: NATURE COMMUNICATIONS
Volume: 10
起始頁: 0
結束頁: 0
顯示於類別:期刊論文