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 1

Consequences of forced expression of the tumor suppressor gene ARHI in ovarian cancer.

Options: View larger image (or click on image) Download as PowerPoint
Consequences of forced expression of the tumor suppressor gene ARHI in o...
In their study in this issue of the JCI, Lu et al. (8) report that controlled expression of the tumor suppressor gene ARHI in human ovarian cancer cells leads to autophagy. (A) ARHI expression was associated with interrupted PI3K signaling, which resulted in reversible (under conditions of transient ARHI expression) or irreversible (under conditions of chronic ARHI expression) autophagic cell death in vitro. (B) In contrast, ARHI-induced autophagy contributed to cell survival and tumor dormancy in ovarian cancer xenografts in mice, due to partially restored PI3K signaling from elements of the tumor microenvironment.