Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells
Ji Wang, Harilaos Filippakis, Thomas R. Hougard, Heng Du, Chenyang Ye, Heng-Jia Liu, Long Zhang, K.M. Hindi, Shefali Bagwe, Julie Nijmeh, John M. Asara, Wei Shi, Souheil El‐Chemaly, Elizabeth P. Henske, Hilaire C. Lam
Abstract
Significance The tumor suppressor syndrome tuberous sclerosis complex (TSC) affects 1:10,000 live births. We discovered that the inflammatory cytokine Interleukin-6 (IL-6) promotes the proliferation and migration of TSC2-deficient cells in part through the regulation of PSAT1 and de novo serine biosynthesis. Importantly, IL-6 neutralizing antibody treatments reduced renal cyst and cystadenoma formation in Tsc2 +/− mice. This study highlights a therapeutically targetable vulnerability of TSC, which may have broad clinical application to mTORC1-activated tumors.