PERK-mediated expression of peptidylglycine α-amidating monooxygenase supports angiogenesis in glioblastoma

• Verfasst von: Soni, Himanshu [VerfasserIn]
• Verfasst von: Tews, Björn [VerfasserIn]
• Verfasst von: Goidts, Violaine [VerfasserIn]
• Titel: PERK-mediated expression of peptidylglycine α-amidating monooxygenase supports angiogenesis in glioblastoma
• Verf.angabe: Himanshu Soni, Julia Bode, Chi D. L. Nguyen, Laura Puccio, Michelle Neßling, Rosario M. Piro, Jonas Bub, Emma Phillips, Robert Ahrends, Betty A. Eipper, Björn Tews and Violaine Goidts
• E-Jahr: 2020
• Jahr: 13 February 2020
• Umfang: 16 S.
• Fussnoten: Gesehen am 31.03.2020
• Titel Quelle: Enthalten in: Oncogenesis
• Ort Quelle: [Erscheinungsort nicht ermittelbar] : Nature Publ., 2012
• Jahr Quelle: 2020
• Band/Heft Quelle: 9(2020,2) Artikel-Nummer 18, 16 Seiten
• ISSN Quelle: 2157-9024
• DOI: doi:10.1038/s41389-020-0201-8
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1693624036

Abstract

PKR-like kinase (PERK) plays a significant role in inducing angiogenesis in various cancer types including glioblastoma. By proteomics analysis of the conditioned medium from a glioblastoma cell line treated with a PERK inhibitor, we showed that peptidylglycine α-amidating monooxygenase (PAM) expression is regulated by PERK under hypoxic conditions. Moreover, PERK activation via CCT020312 (a PERK selective activator) increased the cleavage and thus the generation of PAM cleaved cytosolic domain (PAM sfCD) that acts as a signaling molecule from the cytoplasm to the nuclei. PERK was also found to interact with PAM, suggesting a possible involvement in the generation of PAM sfCD. Knockdown of PERK or PAM reduced the formation of tubes by HUVECs in vitro. Furthermore, in vivo data highlighted the importance of PAM in the growth of glioblastoma with reduction of PAM expression in engrafted tumor significantly increasing the survival in mice. In summary, our data revealed PAM as a potential target for antiangiogenic therapy in glioblastoma.