Tuberin Regulates Prostaglandin Receptor-Mediated Viability, via Rheb, in mTORC1-Hyperactive Cells

In this study, we identify upregulation of EP3 (PTGER3) expression in TSC2-deficient cells, TSC renal angiomyolipomas, lymphangioleiomyomatosis lung nodules, and epileptic brain tubers. TSC2 negatively regulated EP3 expression via Rheb in a rapamycin-insensitive manner. The EP3 antagonist, L-798106, selectively suppressed the viability of TSC2-deficient cells in vitro and decreased the lung colonization of TSC2-deficient cells. Collectively, these data reveal a novel function of TSC2 and Rheb in the regulation of EP3 expression and cell viability.
Implications: Therapeutic targeting of an aberrant PGE2-EP3 signaling axis may have therapeutic benefit for TSC patients and for other mTOR-hyperactive neoplasms. Mol Cancer Res; 15(10); 1318–30. ©2017 AACR.

Source: Molecular Cancer Research - October 1, 2017 Category: Cancer & Oncology Authors: Li, C., Liu, X., Liu, Y., Zhang, E., Medepalli, K., Masuda, K., Li, N., Wikenheiser-Brokamp, K. A., Osterburg, A., Borchers, M. T., Kopras, E. J., Plas, D. R., Sun, J., Franz, D. N., Capal, J. K., Mays, M., Sun, Y., Kwiatkowski, D. J., Alayev, A., Holz, M Tags: Cell Death and Survival Source Type: research