Transcription factor YY1 enhances the stemness of lung cancer cells by stabilizing hypoxia factor HIF-1α under a hypoxic microenvironment

Lung Cancer
04/09/2020

Environ Toxicol. 2020 Sep 3. doi: 10.1002/tox.23017. Online ahead of print.

ABSTRACT

The hypoxic microenvironment can facilitate the tumor progression, and transcription factor YY1 holds promoting effects in various tumors. This work aims to investigate whether YY1 is involved in hypoxia-induced stemness of lung cancer cells. We showed that hypoxic microenvironment induced the expression of HIF-1α and YY1, and the stemness of lung cancer cells, which was attenuated by YY1 knockdown. Additionally, we found that YY1 regulates the hypoxia-induced stemness in a HIF-1α-dependent


manner, but independent on p53 expression. Further analysis revealed that YY1 physically interacted with HIF-1α protein and stabilized HIF-1α protein. Our work indicates a novel YY1/HIF-1α axis regulating the stemness of lung cancer cells.