Resistance of glioma cells to nutrient-deprived microenvironment can be enhanced by CD133-mediated autophagy

Abstract

CD133 is a pentaspan transmembrane protein that can serve as a biomarker for cancer stem cells, although its biochemical mechanism remains unclear. Here we report that CD133 expression enhances glioma cell tolerance of a nutrient-deprived microenvironment. Under starvation conditions, CD133-positive cells exhibited higher survival and decreased levels of apoptosis. These changes were dependent on activation of autophagy-associated gene signaling and were impaired by the autophagic inhibitor chloroquine. Furthermore, rapamycin up-regulated the level of autophagy and inversely reduced CD133 expression. Immunofluorescence confirmed that starvation promoted release of CD133 from the plasma membrane to the cytoplasm, with CD133 also partially co-localizing with LC3 upon starvation. Additionally, CD133 partially co-localized with Beclin1, Atg5, and lysosomes, indicating that CD133 directly participates in the autophagosome membrane fusion process and ultimately undergoes lysosomal degradation. Collectively, our results demonstrate that CD133 contributes to cell survival by regulating autophagy, and that targeting CD133-linked signaling and autophagy may be useful in improving anti-cancer treatments.

Insufficient radiofrequency ablation promotes hepatocellular carcinoma cell progression via autophagy and the CD133 feedback loop

“…Notably, CD133 has been indicated to improve the resistance of glioma cells to a nutrient-deprived microenvironment by participating in autophagosome biogenesis ( 33 ). Meanwhile, Chen et al ( 24 ) found that CD133 is involved in cell survival through regulation of autophagy and glucose uptake in HCC.…”

Differences of basic and induced autophagic activity between K562 and K562/ADM cells

“…A report has described that activation of autophagy is critical for cancer cellular survival under nutrient starvation (39). Another report also demonstrates that CD133-positive glioma cells exhibit higher survival under starvation conditions, which depends on induction of autophagy (40). Furthermore, autophagy induced by amino acid starvation is accelerated in the multidrug-resistant cells when compared to parental cells, resulting in enhanced cell survival capacity (41).…”

Glioma cells are resistant to inflammation‑induced alterations of mitochondrial dynamics

“…During tumorigenesis, decreased mitophagy may lead to the persistence of damaged mitochondria in cells, which may result in higher levels of tumor-promoting ROS or other mitochondrial signals (25). By contrast, established tumors may require mitophagy for stress adaptation and survival (25,27,28). Despite the multitude of mechanisms that have been proposed to explain the mitochondrial dynamics in tumor cells, the effects of inflammation on this cellular event in glioma remain uncharacterized.…”