Expression of activator proteins of SHH/GLI and PI3K/Akt/mTORC1 signaling pathways in human gliomas is associated with high grade tumors. 2021

Julián Henao-Restrepo, and Yudys Anggelly Caro-Urrego, and Lina Marcela Barrera-Arenas, and Juan Carlos Arango-Viana, and Maria Bermudez-Munoz
Institute of Biology, Faculty of Exact and Natural Sciences, University of Antioquia, Calle 67 #53-108, 050010 Medellín, Colombia. Electronic address: julian.henaor@udea.edu.co.

Recent findings have demonstrated a synergic crosstalk between SHH/GLI and PI3K/Akt/mTORC1 signaling in glioblastoma progression cells in vitro and in tumors in mice, but it is not known if this also occurs in human gliomas. We then aimed to investigate the expression of key proteins of these pathways in different human gliomas. The expression of PTEN, phospho-Akt (Ser473), phospho-S6K1 (Thr389), SHH, GLI1, GLI2 and GLI3 was assessed by immunohistochemistry in gliomas and in control brain tissues. The pattern of expression of each protein was established according to glioma type, glioma grade and to cell type; the relative expression of each protein was used to perform statistical analyses. We found that the expression of proteins of both signaling pathways differs between normal brain and glioma tissues. For instance, normal astrocytes had a different protein expression pattern compared with reactive and tumoral astrocytes. Interestingly, we detected a recurrent pattern of expression of GLI3 in oligodendrocytes and of phospho-S6K1 in mitotic neoplastic cells. We also identified differences of cell signaling according to glioma type: oligodendrogliomas and ependymomas are related with the expression of SHH/GLI proteins. Finally, we detected that high grade gliomas statistically correlate with the expression of GLI1 and GLI2, and that GLI1, GLI2, phospho-Akt and phospho-S6K1 are more expressed in patients with less survival, suggesting that activation of these cell signaling influences glioma outcome and patient survival. In summary, our results show that proteins of PI3K/Akt/mTORC1 and SHH/GLI pathways are differentially expressed in human gliomas according to tumor type and grade, and suggest that the activation of these signaling networks is associated with glioma progression.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D005260 Female Females
D005910 Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21) Glial Cell Tumors,Malignant Glioma,Mixed Glioma,Glial Cell Tumor,Glioma, Malignant,Glioma, Mixed,Gliomas,Gliomas, Malignant,Gliomas, Mixed,Malignant Gliomas,Mixed Gliomas,Tumor, Glial Cell,Tumors, Glial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071676 Zinc Finger Protein GLI1 A transcriptional activator and oncogene protein that contains two CYS2-HIS2 ZINC FINGERS. Two isoforms are expressed; both regulate the expression of specific genes during development of craniofacial features, digits, the CENTRAL NERVOUS SYSTEM; and the GASTROINTESTINAL TRACT. They also regulate SONIC HEDGEHOG PROTEIN signaling and cell proliferation. Gli Protein,Gli1 Protein,Glioma-Associated Oncogene Protein,Oncogene GLI Protein,GLI Protein, Oncogene,Glioma Associated Oncogene Protein,Oncogene Protein, Glioma-Associated
D000076222 Mechanistic Target of Rapamycin Complex 1 An evolutionarily conserved multiprotein complex that functions as a cellular energy sensor and regulator of protein synthesis for cell growth and proliferation. It consists of TOR SERINE-THREONINE KINASES; REGULATORY-ASSOCIATED PROTEIN OF MTOR (RAPTOR); MLST8 PROTEIN; and AKT1 substrate 1 protein. The activity of the complex is regulated by SIROLIMUS; INSULIN; GROWTH FACTORS; PHOSPHATIDIC ACIDS; some amino acids or amino acid derivatives, and OXIDATIVE STRESS. TOR Complex 1,TORC1,Target of Rapamycin Complex 1,mTORC1,mTORC1 Complex,Complex, mTORC1
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic

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