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

Cancers

Anne Vehlow¹  Nils Cordes¹  Stefanie Moritz¹  Jessica Schlatter²  Matthias Krause² 

[1] OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, PF 41, 01307 Dresden, Germany;Randall Centre of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London SE1 1UL, UK;

关键词: Lamellipodin;    glioblastoma;    invasion;    radiosensitivity;    RICTOR;    EGFR;   

DOI  :  10.3390/cancers13215337

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown