Slug Is Associated With Tumor Metastasis and Angiogenesis in Ovarian Cancer

Abstract

Ovarian cancer is the most lethal gynecologic malignancy among women and usually initiated by the malignant transformation of epithelial cells. The progression of ovarian cancer involves a cascade of events, including tumor cell epithelial-mesenchymal transition (EMT), invasion, migration, and angiogenesis. Slug plays vital roles in the development of motile and invasive manner of cancer cells via EMT progression. The present work is devoted to investigate the effect of slug on the invasion and angiogenesis in ovarian cancer. The findings reveal that tumors with high expression of slug (44 of 60) represent higher tumor grade, lymph node metastasis, and worse prognosis than those with low expression (16 of 60; P < .05). We also identified a significant correlation between the slug and the microvessel density (MVD). Results of transwell migration assay showed that decreased slug induced by short hairpin RNA contributed to the repressed invasion and migration of SKOV3 cells. Additionally, the migration and tube formation capacity of human umbilical vein endothelial cells were markedly decreased in SKOV3-sh-conditioned medium compared to SKOV3 and SKOV3-NC. Furthermore, xenograft mouse models (SKOV3/SKOV3-sh cells injection into BALB/c nude mice) were developed to validate the effects of slug. The data confirmed that inhibited expression of slug extensively decreased the growth of tumor and MVD in vivo. Moreover, knockdown of slug can significantly reduce tumor angiogenesis of SKOV3 cells via ccn1/vascular endothelial growth factor. Thus, our present study demonstrates that slug is closely associated with tumor metastasis and angiogenesis in ovarian cancer.

Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway

“…Among them, Slug is closely associated with tumor metastasis in ovarian cancer [28]. In the present study, Slug has identified specific mechanisms controlled during EMT in the A2780 and SK-OV-3 cells.…”

miR-151a enhances Slug dependent angiogenesis

“…It is well established that Slug is a key transcription factor implicated in angiogenesis and the EndoMT transition by repressing E-Cad expression and inducing N-Cad expression, thereby effectively regulating the transition between EMT and MET [38,39]. Slug has been reported to be overexpressed in many types of cancer, including lung cancer [40][41][42][43][44][45][46]. In addition, it is known that the family of EMT-TFs can be activated by a myriad of receptors and signaling pathways including tumor growth factor TFGβ, Notch, Wnt, morphogenetic protein BMPs, Ras/Erk pathways as well as inflammation, hypoxia and shear stress forces, and that the EMT-TF can also regulate each other in complex and interdependent ways [12,47].…”

Melatonin suppresses chronic restraint stress-mediated metastasis of epithelial ovarian cancer via NE/AKT/β-catenin/SLUG axis

“…EMT-related transcription factors play important roles in cancer dissemination. Previous studies indicate that many of these factors, including TWIST 18 , SLUG 19 , and β-catenin 20 , act synergistically and reciprocally with one another and use common pathways (reviewed in 21 ), which are associated with poor prognosis of EOC. Then we conducted immunofluorescence (IF) staining to examine whether CRS affected expression of these factors in tumor tissues.…”