Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR

Glioblastoma is a tumor type of unmet need despite the development of multimodal treatment strategies. The main factors contributing to the poor prognosis of glioblastoma patients are diverse genetic and epigenetic changes driving glioblastoma persistence and recurrence. Complemented are these facto...

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Autores principales:	Stefanie Moritz, Matthias Krause, Jessica Schlatter, Nils Cordes, Anne Vehlow
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Lamellipodin glioblastoma invasion radiosensitivity RICTOR EGFR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/be5b6dd7ff5841eb82cee43816317289
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spelling	oai:doaj.org-article:be5b6dd7ff5841eb82cee438163172892021-11-11T15:28:40ZLamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR10.3390/cancers132153372072-6694https://doaj.org/article/be5b6dd7ff5841eb82cee438163172892021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5337https://doaj.org/toc/2072-6694Glioblastoma is a tumor type of unmet need despite the development of multimodal treatment strategies. The main factors contributing to the poor prognosis of glioblastoma patients are diverse genetic and epigenetic changes driving glioblastoma persistence and recurrence. Complemented are these factors by extracellular cues mediated through cell surface receptors, which further aid in fostering pro-invasion and pro-survival signaling contributing to glioblastoma therapy resistance. The underlying mechanisms conferring this therapy resistance are poorly understood. Here, we show that the cytoskeleton regulator Lamellipodin (Lpd) mediates invasiveness, proliferation and radiosensitivity of glioblastoma cells. Phosphoproteome analysis identified the epidermal growth factor receptor (EGFR) signaling axis commonly hyperactive in glioblastoma to depend on Lpd. Mechanistically, EGFR signaling together with an interaction between Lpd and the Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) jointly regulate glioblastoma radiosensitivity. Collectively, our findings demonstrate an essential function of Lpd in the radiation response and invasiveness of glioblastoma cells. Thus, we uncover a novel Lpd-driven resistance mechanism, which adds an additional critical facet to the complex glioblastoma resistance network.Stefanie MoritzMatthias KrauseJessica SchlatterNils CordesAnne VehlowMDPI AGarticleLamellipodinglioblastomainvasionradiosensitivityRICTOREGFRNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5337, p 5337 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lamellipodin glioblastoma invasion radiosensitivity RICTOR EGFR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Lamellipodin glioblastoma invasion radiosensitivity RICTOR EGFR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Stefanie Moritz Matthias Krause Jessica Schlatter Nils Cordes Anne Vehlow Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR
description	Glioblastoma is a tumor type of unmet need despite the development of multimodal treatment strategies. The main factors contributing to the poor prognosis of glioblastoma patients are diverse genetic and epigenetic changes driving glioblastoma persistence and recurrence. Complemented are these factors by extracellular cues mediated through cell surface receptors, which further aid in fostering pro-invasion and pro-survival signaling contributing to glioblastoma therapy resistance. The underlying mechanisms conferring this therapy resistance are poorly understood. Here, we show that the cytoskeleton regulator Lamellipodin (Lpd) mediates invasiveness, proliferation and radiosensitivity of glioblastoma cells. Phosphoproteome analysis identified the epidermal growth factor receptor (EGFR) signaling axis commonly hyperactive in glioblastoma to depend on Lpd. Mechanistically, EGFR signaling together with an interaction between Lpd and the Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) jointly regulate glioblastoma radiosensitivity. Collectively, our findings demonstrate an essential function of Lpd in the radiation response and invasiveness of glioblastoma cells. Thus, we uncover a novel Lpd-driven resistance mechanism, which adds an additional critical facet to the complex glioblastoma resistance network.
format	article
author	Stefanie Moritz Matthias Krause Jessica Schlatter Nils Cordes Anne Vehlow
author_facet	Stefanie Moritz Matthias Krause Jessica Schlatter Nils Cordes Anne Vehlow
author_sort	Stefanie Moritz
title	Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR
title_short	Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR
title_full	Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR
title_fullStr	Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR
title_full_unstemmed	Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR
title_sort	lamellipodin-rictor signaling mediates glioblastoma cell invasion and radiosensitivity downstream of egfr
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/be5b6dd7ff5841eb82cee43816317289
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Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR

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