Unknown

Dataset Information

0

HYSK1 promotes cancer cell proliferation and migration through negative regulation of p16INK4a under hypoxic conditions.


ABSTRACT: The alteration of expression of p16INK4a, a well-known cyclin-dependent kinase inhibitor involved in cell cycle control, in tumors is unclear, especially under hypoxic conditions. To evaluate p16INK4a 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 p16INK4a. 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 p16INK4a under hypoxic conditions in tumors, where it negatively regulates p16INK4a, enhancing cancer cell migration. Hypoxic stimulation of hYSK1 reduces p16INK4a 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 p16INK4a expression and suppressed MMP-2 expression. Thus, hYSK1 is necessary as a trigger for inactivating p16INK4a and activating MMP-2 during tumor migration, suggesting that hYSK1 is a specific negative regulator of the tumor suppressor p16INK4a and may represent a novel molecular target for reactivation of tumor suppressor genes in humans.

SUBMITTER: Lee MH 

PROVIDER: S-EPMC5687670 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

hYSK1 promotes cancer cell proliferation and migration through negative regulation of p16<sup>INK4a</sup> under hypoxic conditions.

Lee Mee-Hyun MH   Dong Zigang Z   Surh Young-Joon YJ   Choi Bu Young BY  

Oncotarget 20171006 51


The alteration of expression of p16<sup>INK4a</sup>, a well-known cyclin-dependent kinase inhibitor involved in cell cycle control, in tumors is unclear, especially under hypoxic conditions. To evaluate p16<sup>INK4a</sup> 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<sup>INK4a</sup>. hYSK1, a member of the Ste20 family of serine/threonine protein kinases, promotes cel  ...[more]

Similar Datasets

| S-EPMC5663593 | biostudies-literature
| S-EPMC7674439 | biostudies-literature
| S-EPMC7415903 | biostudies-literature
| S-EPMC3752612 | biostudies-literature
| S-EPMC3217078 | biostudies-literature
| S-EPMC6476958 | biostudies-literature
| S-EPMC6646234 | biostudies-literature
| S-EPMC4394754 | biostudies-literature
| S-EPMC3822700 | biostudies-literature
| S-EPMC6946778 | biostudies-literature