Targeting HIF-1a Function in Cancer through the Chaperone Action of NQO1: Implications of Genetic Diversity of NQO1

Salido, Eduardo ; Timson, David J. ; Betancor-Fernández, Isabel ; Palomino-Morales, Rogelio ; Anoz-Carbonell, Ernesto ; Pacheco-García, Juan Luis ; Medina, Milagros (Universidad de Zaragoza) ; Pey, Ángel L.

Resumen: HIF-1a is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1a inhibition represents an interesting target for anti-cancer therapy. It was recently shown that the HIF-1a interaction with NQO1 inhibits proteasomal degradation of the former, thus suggesting that targeting the stability and/or function of NQO1 could lead to the destabilization of HIF-1a as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1a are beginning to be unraveled, in this review we discuss: (1) Structure–function relationships of HIF-1a; (2) our current knowledge on the intracellular functions and stability of NQO1; (3) the pharmacological modulation of NQO1 by small ligands regarding function and stability; (4) the potential effects of genetic variability of NQO1 in HIF-1a levels and function; (5) the molecular determinants of NQO1 as a chaperone of many different proteins including cancer-associated factors such as HIF-1a, p53 and p73a. This knowledge is then further discussed in the context of potentially targeting the intracellular stability of HIF-1a by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies, always considering that the substantial genetic variability in NQO1 would likely result in different phenotypic responses among individuals.

Idioma: Inglés

DOI: 10.3390/jpm12050747

Año: 2022

Publicado en: Journal of Personalized Medicine 12, 5 (2022), [28 pp.]
ISSN: 2075-4426

Factor impacto JCR: 3.4 (2022)

Categ. JCR: MEDICINE, GENERAL & INTERNAL rank: 67 / 169 = 0.396 (2022) - Q2 - T2
Categ. JCR: HEALTH CARE SCIENCES & SERVICES rank: 42 / 107 = 0.393 (2022) - Q2 - T2

Factor impacto CITESCORE: 2.6 - Medicine (Q3)

Factor impacto SCIMAGO: 0.665 - Medicine (miscellaneous) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2019-110900GB-I00
Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)