Autophagy-induced tumor dormancy in ovarian cancer
Ravi K. Amaravadi
Ravi K. Amaravadi
Published November 20, 2008
Citation Information: J Clin Invest. 2008;118(12):3837-3840. https://doi.org/10.1172/JCI37667.
View: Text | PDF
Commentary

Autophagy-induced tumor dormancy in ovarian cancer

Abstract

Autophagy — a process of “self-eating” that involves enzymatic digestion and recycling of cellular constituents in response to stress — contributes to both cancer cell death and survival. In this issue of the JCI, Lu et al. report that controlled induction of tumor suppressor gene aplasia Ras homolog member I (ARHI) results in autophagic cell death of human ovarian cancer cells in vitro (see the related article beginning on page 3917). However, within xenograft tumors in mice, multiple factors within the tumor microenvironment switched ARHI-induced autophagy to a mechanism of tumor cell survival, leading to tumor dormancy. Since ARHI expression is suppressed in the majority of breast and ovarian cancers but is high in premalignant lesions, ARHI-induced autophagy could be manipulated for therapeutic benefit.

Authors

Ravi K. Amaravadi

×

Figure 2

The magnitude of autophagy may determine the fate of cancer cells in vivo.

Options: View larger image (or click on image) Download as PowerPoint
The magnitude of autophagy may determine the fate of cancer cells in viv...
This conceptual model proposes a relationship between the magnitude of cancer cell autophagy and its consequences on cell death and cell survival. As reported by Lu et al., expression of the tumor suppressor gene ARHI suppresses signal transduction through PI3K signaling, while factors within the tumor microenvironment maintain PI3K signaling within tumor cells (8). The magnitude of autophagy may be inversely proportional to PI3K signaling, and thresholds may exist within cancer cells for the magnitude of autophagy that leads to cell death versus the magnitude of autophagy that leads to cell survival.