NQO1 Is Regulated by PTEN in Glioblastoma, Mediating Cell Proliferation and Oxidative Stress

Abstract EN

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a dismal prognosis, and the patients carrying EGFR-driven tumors with PTEN mutation do not respond to anti-EGFR therapy.

The molecular mechanisms for this resistance remain unknown.

Here, we show that PTEN induces the expression of NQO1, a flavoenzyme with dual roles in pro- and antitumorigenesis that decreases the formation of reactive oxygen species (ROS), which mediates the oxidative stress and GBM cell proliferation.

NQO1 is reduced in EGFRvIII-overexpressed U87MG cells associated with low ROS, whereas NQO1 is highly escalated in PTEN stably expressed U87MG/EGFRvIII cells with high ROS.

Interestingly, knockdown of NQO1 augments ROS and diminishes cell proliferation.

Conversely, overexpression of NQO1 attenuates ROS and increases cell proliferation.

By contrast, overexpression of PINK1, a PTEN-induced kinase 1, represses ROS and inhibits GBM cell proliferation.

Therefore, our findings support that NQO1 displays a paradoxical role in mediating GBM growth in response to tumor suppressor PTEN.