Type 1 Insulin-Like Growth Factor Receptor (IGF1R) Nuclear Localization in High-grade Glioma cells enhances Motility, Metabolism and in vivo Tumorigenesis

AYELEN MARTIN; MARÍA CELIA FERNANDEZ; ELIZABETH R. CATTANEO; CLAUDIO DAVID SCHUSTER; FLORENCIA CLÉMENT; MARCELA VENARA; ARIEL BERENSTEIN; MERCEDES GARCÍA LOMBARDI; IGNACIO BERGADÁ; MARIANA GUTIERREZ; MARCELO MARTÍ; MARÍA R. GONZALEZ-BARO; PATRICIA PENNISI

Frontiers in Endocrinology

Frontiers Media

Año: 2022

Gliomas are the most frequent solid tumors in children. Among these, high-grade gliomas are less20 common in children than in adults, though are similar in their aggressive clinical behavior. In adults,21 glioblastoma is the most lethal tumor of the central nervous system. The insulin-like growth factor 122 receptor (IGF1R) plays an important role in cancer biology, and its nuclear localization has been23 described as an adverse prognostic factor in different tumors. Previously, we have demonstrated that24 in pediatric gliomas, IGF1R nuclear localization is significantly associated with high-grade tumors,25 worst clinical outcome and increased risk of death. Herein, we explore the role of IGF1R intracellular26 localization comparing two glioblastoma cell lines that differ only in the IGF1R capacity to27 translocate to the nucleus. In vitro, IGF1R nuclear localization enhances glioblastoma cell motility28 and metabolism without affecting their proliferation. In vivo, IGF1R capacity to translocate to the29 nucleus allows not only a higher proliferation rate and earlier development of tumors, but also30 renders the cells sensitive to OSI906 therapy. With this work we provide evidence supporting the31 implications of the presence of IGF1R in the nucleus of glioma cells, and a potential therapeutic32 opportunity for patients harboring gliomas with IGF1R nuclear localization