Backgound. We investigated malic enzyme expression and the induction of senescence in head and neck squamous cells carcinoma (HNSCC).

p53, malic enzyme 1 (ME1) and ME2, and aspects of cellular metabolism such as reactive oxygen species (ROS) were investigated in HNSCC cell lines.

Both metformin and ionizing radiation inhibited the expression of ME2, but not ME1, in HNSCC. Knockdown of ME1 or ME2 potentiated therapy-induced senescence (TIS) in HNSCC cells regardless of p53 status, and led to increased p21 and generation of ROS. TIS in ME-depleted cells was blocked by the antioxidant N-acetyl cysteine. Finally, high expression of ME2 was associated poorer overall survival in HNSCC patients.

Depletion of ME enhances TIS and seems driven largely by ROS. ME2 expression in HNSCC may be associated with poor outcome, providing a possible link between therapy-induced senescence and patient outcome and indicating potential therapeutic benefit of targeting ME2. This article is protected by copyright. All rights reserved.