Autophagy and TrkC/NT-3 signaling joined forces boost the hypoxic glioblastoma cell survival.

Glioblastoma multiform (GBM), the most common and aggressive primary brain tumor, is characterized by a high degree of hypoxia and resistance to therapy because of its adaptation capacities, including autophagy and growth factors signaling. In this study, we show an efficient hypoxia-induced survival autophagy in four different GBM cell lines (U87MG, M059K, M059J and LN-18) and an activation of a particular neurotrophin signaling pathway. Indeed, the enhancement of both TrkC and NT-3 was followed by downstream p38MAPK phosphorylation, suggesting the occurrence of a survival autocrine loop.

Glioblastoma, hypoxia and autophagy: a survival-prone 'ménage-à-trois'.

Glioblastoma multiforme is the most common and the most aggressive primary brain tumor. It is characterized by a high degree of hypoxia and also by a remarkable resistance to therapy because of its adaptation capabilities that include autophagy. This degradation process allows the recycling of cellular components, leading to the formation of metabolic precursors and production of adenosine triphosphate.

KLRC3, a Natural Killer receptor gene, is a key factor involved in glioblastoma tumourigenesis and aggressiveness.

Glioblastoma is the most lethal brain tumour with a poor prognosis. Cancer stem cells (CSC) were proposed to be the most aggressive cells allowing brain tumour recurrence and aggressiveness. Current challenge is to determine CSC signature to characterize these cells and to develop new therapeutics.

Autophagy takes place in mutated p53 neuroblastoma cells in response to hypoxia mimetic CoCl(2).

Solid tumors like neuroblastoma exhibit hypoxic areas, which can lead both to cell death or aggressiveness increase. Hypoxia is a known stress able to induce stabilization of p53, implicated in cell fate regulation. Recently, p53 appeared to be involved in autophagy in an opposite manner, depending on its location: when nuclear, it enhanced transcription of pro-autophagic genes whereas when cytoplasmic, it inhibited the autophagic process.