Secretome analysis of glioblastoma cells

ABSTRACT: PKR-like kinase (PERK) plays a significant role in inducing angiogenesis in various cancer-types including glioblastoma. Mass spectrometry screen on conditioned media from LN308 glioblastoma cell line treated with hypoxia revealed Peptidylglycine α-amidating monooxygenase (PAM) as a potential target inducing angiogenesis. PERK is found to be regulating PAM at mRNA level. PERK activation via CCT020312 (PERK activator) also increased the cleavage and thus the generation of sfCD domain of PAM in an oxygen-independent manner which acts as a signaling molecule from cytoplasm to the nuclei. PERK was found interacting with PAM in immuno-precipitation experiments suggesting a possible involvement in the generation of the PAM sfCD domain. Knockdown of PERK or PAM in LN308 cells reduced the formation of tubes by HUVECs in vitro. In vivo data also highlighted the importance of PAM in growth of glioblastoma where reduction of PAM expression in engrafted tumor significantly increased the survival in mice. In summary, PAM acts as a potential target for therapy against angiogenesis in glioblastoma.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Chi Nguyen  

LAB HEAD: Robert Ahrends

PROVIDER: PXD012523 | Pride | 2020-03-05

REPOSITORIES: Pride