RGS12 is a novel tumor suppressor in osteosarcoma that inhibits YAP-TEAD1-Ezrin signaling.

Abstract	Osteosarcoma (OS) is the most common primary malignancy of the bone that predominantly affects children and adolescents. Hippo pathway is a crucial regulator of organ size and tumorigenesis. However, how Hippo pathway regulates the occurrence of osteosarcoma is largely unknown. Here, we reported the regulator of G protein signaling protein 12 (RGS12) is a novel Hippo pathway regulator and tumor suppressor of osteosarcoma. Depletion of Rgs12 promotes osteosarcoma progression and lung metastasis in an orthotopic xenograft mouse model. Our data showed that the knockdown of RGS12 upregulates Ezrin expression through promoting the GNA12/13-RhoA-YAP pathway. Moreover, RGS12 negatively regulates the transcriptional activity of YAP/TEAD1 complex through its PDZ domain function to inhibit the expression and function of the osteosarcoma marker Ezrin. PDZ domain peptides of RGS12 can inhibit the development of intratibial tumor and lung metastases. Collectively, this study identifies that the RGS12 is a novel tumor suppressor in osteosarcoma through inhibiting YAP-TEAD1-Ezrin signaling pathway and provides a proof of principle that targeting RGS12 may be a therapeutic strategy for osteosarcoma.
Authors	Yang Li, Min Liu, Shuting Yang, Ashley M Fuller, T S Karin Eisinger-Mathason, Shuying Yang
Journal	Oncogene (Oncogene) Vol. 40 Issue 14 Pg. 2553-2566 (04 2021) ISSN: 1476-5594 [Electronic] England
PMID	33686240 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Cell Cycle Proteins Cytoskeletal Proteins DNA-Binding Proteins Nuclear Proteins RGS Proteins RGS12 protein, human TEA Domain Transcription Factors TEAD1 protein, human Transcription Factors YY1AP1 protein, human ezrin
Topics	Animals Bone Neoplasms (genetics, metabolism, pathology) Cell Cycle Proteins (metabolism) Cell Line, Tumor Cell Movement (physiology) Cytoskeletal Proteins (metabolism) DNA-Binding Proteins (metabolism) Down-Regulation Heterografts Humans Mice Mice, SCID Neoplasm Invasiveness Nuclear Proteins (metabolism) Osteosarcoma (genetics, metabolism, pathology) RGS Proteins (genetics, metabolism) Signal Transduction Survival Analysis TEA Domain Transcription Factors Transcription Factors (metabolism)

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