例如:"lncRNA", "apoptosis", "WRKY"

PSPC1-interchanged interactions with PTK6 and β-catenin synergize oncogenic subcellular translocations and tumor progression.

Nat Commun. 2019 Dec 16;10(1):5716
Yaw-Dong Lang 1 , Hsin-Yi Chen 2 , Chun-Ming Ho 3 , Jou-Ho Shih 1 , En-Chi Hsu 1 , Roger Shen 4 , Yu-Ching Lee 5 , Jyun-Wei Chen 1 , Cheng-Yen Wu 1 , Hsi-Wen Yeh 1 , Ruey-Hwa Chen 6 , Yuh-Shan Jou 7
Yaw-Dong Lang 1 , Hsin-Yi Chen 2 , Chun-Ming Ho 3 , Jou-Ho Shih 1 , En-Chi Hsu 1 , Roger Shen 4 , Yu-Ching Lee 5 , Jyun-Wei Chen 1 , Cheng-Yen Wu 1 , Hsi-Wen Yeh 1 , Ruey-Hwa Chen 6 , Yuh-Shan Jou 7
+ et al

[No authors listed]

Author information
  • 1 Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
  • 2 Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
  • 3 Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei, 11529, Taiwan.
  • 4 Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, 11221, Taiwan.
  • 5 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
  • 6 Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
  • 7 Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, 11221, Taiwan. jou@ibms.sinica.edu.tw.

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 β-catenin, which interacts with PSPC1 to augment Wnt3a autocrine signaling. The aberrant nucleocytoplasmic shuttling of active PTK6/β-catenin is reversed by expressing the PSPC1 C-terminal interacting domain (PSPC1-CT131), thereby suppressing PSPC1/PTK6/β-catenin-activated metastasis to prolong the survival of HCC orthotopic mice. Thus, PSPC1 is the contextual determinant of the oncogenic switch of PTK6/β-catenin subcellular localizations, and PSPC1-CT131 functions as a dual inhibitor of PSPC1 and PTK6 with potential for improving cancer therapy.