Hemoxygenase-1 Promotes Head and Neck Cancer Cell Viability

MASCARÓ, M.; ALONSO, E.G.; SCHWEITZER, K.; RABASSA, M.E.; CARBALLIDO, J.A.; IBARRA, A.; ALONSO, E.N.; BERMÚDEZ, V.; FERNÁNDEZ CHAVEZ, L.; COLÓ, G.P.; FERRONATO, M. J.; PICHEL, P.; RECIO, S.; CLEMENTE, V.; FERMENTO, M.E.; FACCHINETTI, M.M.; CURINO, A.C.

Antioxidants

MDPI

Año: 2022 vol. 11

Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron and biliverdin. We have previously reported that HO-1 protein is upregulated in human HNSCC samples and that it is localized in the cytoplasmic and nuclear compartments; additionally, we have demonstrated that HO-1 nuclear localization is associated with malignant progression. In this work, by using pharmacological and genetic experimental approaches, we begin to elucidate the mechanisms through which HO-1 plays a role in HNSCC. We found that high HO-1 mRNA was associated with decreased patient survival in early stages of HNSCC. In vitro experiments have shown that full-length HO-1 localizes in the cytoplasm, and that, depending on its enzymatic activity, it increases cell viability and promotes cell cycle progression. Instead, HO-1 does not alter migration capacity. Furthermore, we show that C-terminal truncated HO-1 localizes into the nucleus, increases cell viability and promotes cell cycle progression. In conclusion, we herein demonstrate that HO-1 displays protumor activities in HNSCC that depend, at least in part, on the nuclear localization of HO-1.