LIM-homeobox transcription factor 1, alpha (LMX1A) inhibits tumourigenesis, epithelial-mesenchymal transition and stem-like properties of epithelial ovarian cancer

Objective. We reported recently the hypermethylation of LMX1A, a LIM-homeobox gene, as a prognostic biomarker in ovarian cancer; however, the function of LMX1A in ovarian cancer remains unknown. The present study aimed to evaluate the hypothesized tumour-suppressor functions of LMX1A in ovarian cancer. Methods. We analysed the function of LMX1A by examining cell lines, animal models and human ovarian cancer tissues. Overexpression of LMX1A in relation to chemotherapy was also analysed. Results. The expression of LMX1A inhibited cell proliferation, migration, invasion and colony formation in vitro, as well as tumourigenicity in a xenotransplantation mouse model. LMX1A also sensitized ovarian cancer cell lines to chemotherapeutics, and affected epithelial-mesenchymal transition (EMT). The restoration of LMX1A down-regulated stem cell markers and inhibited tumour spheroid formation in SKOV3 cells. Univariate analysis of immunohistochemical staining of tissue arrays (n = 83) revealed that low LMX1A expression was significantly associated with advanced stages (p = 0.001), poor differentiation (p<0.001), early recurrence (p = 0.023) and poor overall survival (p = 0.042) in ovarian cancer. Conclusions. The present study demonstrated, for the first time, that LMX1A is a bona fide tumour suppressor of ovarian cancer. The prognostic values of LMX1A may provide a biomarker for personalized treatments of ovarian cancer patients. The mechanisms of LMX1A in EMT and stem-like properties in ovarian cancer warrant further investigation. (C) 2012 Elsevier Inc. All rights reserved.