Research ArticleCancer

ARD1 Stabilization of TSC2 Suppresses Tumorigenesis Through the mTOR Signaling Pathway

Science Signaling  09 Feb 2010:
Vol. 3, Issue 108, pp. ra9
DOI: 10.1126/scisignal.2000590

You are currently viewing the editor's summary.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Inhibiting mTOR and Tumor Growth

The acetylase arrest-defective protein 1 (ARD1) has been implicated in mammalian cell proliferation and apoptosis, and the dysfunction of these processes contributes to cancer development. Kuo et al. searched an online database for a possible relationship between ARD1 and cancer and found that increased ARD1 mRNA abundance was associated with various measures of improved clinical outcome in patients with breast cancer, suggesting that ARD1 might act as a tumor suppressor. They uncovered ARD1 loss of heterozygosity (LOH) in primary breast cancer and several different cancer cell lines. Further analysis indicated that ARD1 acetylated—and thereby stabilized—tuberous sclerosis 2 (TSC2), part of a complex that inhibits signaling through the mammalian target of rapamycin (mTOR) pathway, a master regulator of cellular metabolism. ARD1-dependent inhibition of mTOR signaling decreased cell proliferation and increased autophagy, thereby suppressing tumor growth in nude mice. Moreover, ARD1 abundance correlated with that of TSC2 in various types of cancer. The authors thus propose that ARD1 suppressed development of multiple types of cancer through its stabilization of TSC2 and the consequent inhibition of mTOR signaling.