Background: New adjuvant therapies for human head and neck (H&N) cancer to improve the quality of
life of the patients are in great demand. Our early studies have demonstrated that uncoupling protein 2
(UCP2) is upregulated in the tumor tissues of H&N cancer compared to the adjacent normal tissues;
however, the role of UCP2 in H&N cancer has not been studied.
Objective: In this manuscript, we aim to examine whether UCP2 contributes to H&N cancer progression
in vitro.
Methods: We generated UCP2 stable knockdown H&N cancer cells and detected the effects of UCP2
inhibition on cell proliferation, migration, invasion, 3D spheroid formation, and the sensitivity to a chemodrug treatment.
Results: Knockdown of UCP2 suppressed the progression of H&N cancer in vitro, which might be mediated
via the following mechanism: 1) increased the G1 phase whereas decreased the S phase of the cell cycle,
which could be mediated by suppression of the G1/S regulators including CDK4/6 and cyclin D1. 2)
Decreased mitochondrial oxygen consumption, ATP production, and lactate formation, which is consistent
with the downregulation of c-Myc. 3) FAK may serve as the upstream signaling molecule, and its action
was mediated by Akt and ERK.
Conclusions: Our studies first demonstrate that targeting UCP2 may suppress H&N cancer progression in
vitro.
Targeting UCP2 Suppresses the FAK Signaling and Progression of Human Head and Neck Cancer Cells
