Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells
Por:
Jiménez-Castillo V., Illescas-Barbosa D., Zenteno E., Ávila-Curiel B.X., Castañeda-Patlán M.C., Robles-Flores M., De Oca D.M.-M., Pérez-Campos E., Torres-Rivera A., Bouaboud A., Pagesy P., Solórzano-Mata C.J., Issad T.
Publicada:
1 ene 2022
Categoría:
Multidisciplinary
Resumen:
O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation. © 2022, The Author(s).
Filiaciones:
Jiménez-Castillo V.:
National Technology of Mexico/IT.Oaxaca, Oaxaca, Mexico
Faculty of Medicine and Surgery, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Faculty of Dentistry, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Illescas-Barbosa D.:
Faculty of Medicine and Surgery, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Faculty of Dentistry, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Zenteno E.:
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
Ávila-Curiel B.X.:
Faculty of Medicine and Surgery, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Faculty of Dentistry, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Castañeda-Patlán M.C.:
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
Robles-Flores M.:
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
De Oca D.M.-M.:
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Pérez-Campos E.:
National Technology of Mexico/IT.Oaxaca, Oaxaca, Mexico
Torres-Rivera A.:
Tecnológico de Estudios Superiores de Huixquilucan, Magdalena Chichicaspa, Mexico
Bouaboud A.:
Université Paris Cité, Institut Cochin, INSERM, CNRS, Paris, 75014, France
Pagesy P.:
Université Paris Cité, Institut Cochin, INSERM, CNRS, Paris, 75014, France
Solórzano-Mata C.J.:
Faculty of Medicine and Surgery, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Faculty of Dentistry, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico
Issad T.:
Université Paris Cité, Institut Cochin, INSERM, CNRS, Paris, 75014, France
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