Browse

hYSK1 promotes cancer cell proliferation and migration through negative regulation of p16INK4a under hypoxic conditions

Cited 2 time in Web of Science Cited 2 time in Scopus
Authors
Lee, Mee-Hyun; Dong, Zigang; Surh, Young-Joon; Choi, Bu Young
Issue Date
2017-10
Citation
Oncotarget, Vol.8 No.51, pp.89072-89085
Keywords
hYSK1p16(INK4a)MMP-2tumor migrationhypoxia
Abstract
The alteration of expression of p16(INK4a), a well-known cyclin-dependent kinase inhibitor involved in cell cycle control, in tumors is unclear, especially under hypoxic conditions. To evaluate p16(INK4a) regulation, we performed a protein microarray analysis. Among 1,800 proteins in the array, we identified hYSK1 as a novel protein that interacts with the tumor suppressor p16(INK4a). hYSK1, a member of the Ste20 family of serine/threonine protein kinases, promotes cell migration and tumorigenesis and is activated by oxidative stress. However, the molecular mechanisms underlying the oncogenic potential of hYSK1 remain elusive. Here, we report that hYSK1 interacts with p16(INK4a) under hypoxic conditions in tumors, where it negatively regulates p16(INK4a), enhancing cancer cell migration. Hypoxic stimulation of hYSK1 reduces p16(INK4a) accumulation through p16 promoter regulation to interact with unphosporylated SP-1 and increases matrix metalloproteinase-2 (MMP-2) expression by activating the MMP-2 promoter associated with cell migration and proliferation. Conversely, knocking down hYSK1 expression activated p16(INK4a) expression and suppressed MMP-2 expression. Thus, hYSK1 is necessary as a trigger for inactivating p16(INK4a) and activating MMP-2 during tumor migration, suggesting that hYSK1 is a specific negative regulator of the tumor suppressor p16(INK4a) and may represent a novel molecular target for reactivation of tumor suppressor genes in humans.
ISSN
1949-2553
URI
https://hdl.handle.net/10371/172631
DOI
https://doi.org/10.18632/oncotarget.21654
Files in This Item:
There are no files associated with this item.
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse