RRC ID 43629
著者 Huang L, Nakai Y, Kuwahara I, Matsumoto K.
タイトル PRAS40 is a functionally critical target for EWS repression in Ewing sarcoma.
ジャーナル Cancer Res
Abstract Ewing sarcoma family tumors (ESFT) are highly aggressive and highly metastatic tumors caused by a chromosomal fusion between the Ewing sarcoma protein (EWS) with the transcription factor FLI-1. However, expression of the EWS/FLI-1 chimeric oncogene by itself is insufficient for carcinogenesis, suggesting that additional events are required. Here, we report the identification of the Akt substrate PRAS40 as an EWS target gene. EWS negatively regulates PRAS40 expression by binding the 3' untranslated region in PRAS40 mRNA. ESFT cell proliferation was suppressed by treatment with an Akt inhibitor, and ESFT cell proliferation and metastatic growth were suppressed by siRNA-mediated PRAS40 knockdown. Furthermore, PRAS40 knockdown was sufficient to reverse an increased cell proliferation elicited by EWS knockdown. In support of a pathologic role for PRAS40 elevation in EFST, we documented inverse protein levels of EWS and PRAS40 in ESFT cells. Together, our findings suggest that PRAS40 promotes the development of ESFT and might therefore represent a novel therapeutic target in this aggressive disease.
巻・号 72(5)
ページ 1260-9
公開日 2012-3-1
DOI 10.1158/0008-5472.CAN-11-2254
PII 0008-5472.CAN-11-2254
PMID 22241085
MeSH Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Cell Line, Tumor Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Oncogene Proteins, Fusion / metabolism Proto-Oncogene Protein c-fli-1 / metabolism RNA-Binding Protein EWS / metabolism* Sarcoma, Ewing / metabolism*
IF 9.727
引用数 17
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 293(RCB1637)