Suppression of autophagy impedes glioblastoma development and induces senescence. Issue 9 (1st September 2016)

• Record Type: Journal Article
• Authors: Gammoh, Noor; Fraser, Jane; Puente, Cindy; Syred, Heather M.; Kang, Helen; Ozawa, Tatsuya; Lam, Du; Acosta, Juan Carlos; Finch, Andrew J.; Holland, Eric; Jiang, Xuejun
• Is Part Of: Autophagy. Volume 12:Issue 9(2016)
• Page Start: 1431
• Page End: 1439
• Publication Date: 2016-09-01
• Subjects: ATG7 -- autophagy -- brain -- cancer -- glioblastoma -- metabolism -- RCAS -- senescence -- tumor; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2016.1190053
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: The function of macroautophagy/autophagy during tumor initiation or in established tumors can be highly distinct and context-dependent. To investigate the role of autophagy in gliomagenesis, we utilized a KRAS-driven glioblastoma mouse model in which autophagy is specifically disrupted via RNAi against Atg7, Atg13 or Ulk1 . Inhibition of autophagy strongly reduced glioblastoma development, demonstrating its critical role in promoting tumor formation. Further supporting this finding is the observation that tumors originating from Atg7 -shRNA injections escaped the knockdown effect and thereby still underwent functional autophagy. In vitro, autophagy inhibition suppressed the capacity of KRAS -expressing glial cells to form oncogenic colonies or to survive low serum conditions. Molecular analyses revealed that autophagy-inhibited glial cells were unable to maintain active growth signaling under growth-restrictive conditions and were prone to undergo senescence. Overall, these results demonstrate that autophagy is crucial for glioma initiation and growth, and is a promising therapeutic target for glioblastoma treatment.