American Association for Cancer Research
00085472can123947-sup-figleg.pdf (110.19 kB)

Supplementary Figure Legends from Oncogenic NRAS, Required for Pathogenesis of Embryonic Rhabdomyosarcoma, Relies upon the HMGA2–IGF2BP2 Pathway

Download (110.19 kB)
journal contribution
posted on 2023-03-30, 21:35 authored by Zhizhong Li, Yunyu Zhang, Krishnan Ramanujan, Yan Ma, David G. Kirsch, David J. Glass

PDF file - 110K



Embryonic rhabdomyosarcoma (ERMS) is the most common soft-tissue tumor in children. Here, we report the identification of the minor groove DNA-binding factor high mobility group AT-hook 2 (HMGA2) as a driver of ERMS development. HMGA2 was highly expressed in normal myoblasts and ERMS cells, where its expression was essential to maintain cell proliferation, survival in vitro, and tumor outgrowth in vivo. Mechanistic investigations revealed that upregulation of the insulin–like growth factor (IGF) mRNA-binding protein IGF2BP2 was critical for HMGA2 action. In particular, IGF2BP2 was essential for mRNA and protein stability of NRAS, a frequently mutated gene in ERMS. shRNA-mediated attenuation of NRAS or pharmacologic inhibition of the MAP–ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) effector pathway showed that NRAS and NRAS-mediated signaling was required for tumor maintenance. Taken together, these findings implicate the HMGA2–IGFBP2–NRAS signaling pathway as a critical oncogenic driver in ERMS. Cancer Res; 73(10); 3041–50. ©2013 AACR.