Soft-tissue leiomyosarcoma is a mesenchymal tumor with a poor prognosis for which effective therapeutic strategies are lacking. In contrast to other sarcoma types, such as gastrointestinal stromal tumor (GIST), very little is known about the genomic and molecular attributes of soft-tissue leiomyosarcoma, and there are no recognized targets for drug development. In an effort to learn more about this elusive cancer type, we performed genomic studies with array comparative genomics hybridization and gene expression array analysis but failed to gain significant insight. Further investigations, including reverse-phase protein lysate array, tissue microarray immunohistochemistry, and mining of gene expression data, led us to discover a novel phenomenon: mesenchymal-to epithelial transition (MET) in leiomyosarcoma. Clinical correlation studies revealed that MET is associated with longer survival in leiomyosarcoma. In this proposal, three established sarcoma investigational teams from three sister institutes in Houston, Tianjin, and Shanghai will pool resources and experience to provide definitive evidence that MET is a clinically beneficial attribute in soft-tissue leiomyosarcoma.