c-FOS suppresses ovarian cancer progression by changing adhesion

Abstract

Background:C-Fos was initially described as oncogene, but was associated with favourable prognosis in ovarian cancer (OvCa) patients. The molecular and functional aspects underlying this effect are still unknown.Methods:Using stable transfectants of SKOV3 and OVCAR8 cells, proliferation, migration, invasion and apoptotic potential of c-FOS-overexpressing clones and controls were compared. Adherence to components of the extracellular matrix was analysed in static assays, and adhesion to E-selectin, endothelial and mesothelial cells in dynamic flow assays. The effect of c-FOS in vivo was studied after intraperitoneal injection of SKOV3 clones into SCID mice, and changes in gene expression were determined by microarray analysis.Results:Tumour growth after injection into SCID mice was strongly delayed by c-FOS overexpression, with reduction of lung metastases and circulating tumour cells. In vitro, c-FOS had only weak influence on proliferation and migration, but was strongly pro-apoptotic. Adhesion to components of the extracellular matrix (collagen I, IV) and to E-selectin, endothelial and mesothelial cells was significantly reduced in c-FOS-overexpressing OvCa cells. This corresponds to deregulation of adhesion proteins and glycosylation enzymes in microarray analysis.Conclusion:In addition to its known pro-apoptotic effect, c-FOS might influence OvCa progression by changing the adhesion of OvCa cells to peritoneal surfaces.

Prognostic impact of transcription factor Fra-1 in ER-positive breast cancer: contribution to a metastatic phenotype through modulation of tumor cell adhesive properties

“…AP-1-regulated genes include important regulators of invasion, proliferation, differentiation, survival and genes associated with hypoxia and angiogenesis (MildeLangosch 2005). Moreover, we have recently shown the effect of two AP-1 components, Fra-2 and c-Fos, on the adhesive properties and the metastatic potential of breast and ovarian cancer cells, respectively (Schroder et al 2010;Oliveira-Ferrer et al 2014). Regarding the functional role of Fra-1 in breast cancer, there are several experimental studies indicating an association between enhanced Fra-1 expression and proliferation, invasion and motility (Belguise et al 2005).…”

Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

“…c-FOS, a tumor suppressor gene with significant prognostic value in OvCa patients, inhibits metastasis by modulating the adhesive properties of OvCa cells [24]. Under the c-Fos-regulated genes, we found, in addition to classical adhesion molecules, several glycosylation enzymes involved in N-and O-glycosylation as well as in the synthesis and modulation of glycosaminoglycans (GAGs).…”

“…In ovarian cancer, there are recent evidences that chondroitin sulfate as well as diverse enzymes involved in the sulfation process of these structures plays an important role for metastatic spread of tumor cells, to some extent via modulation of their adhesive properties [24,30]. CS is composed of repeating disaccharides of N-acetylgalactosamine (GalNAc) and Dglucuronic acid (GlcA) with different sulfation patterns, mediated by various specific CHSTs: [6,9,15,18,21,23].…”

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

“…RNA samples for microarray analysis were prepared as described previously (43,44). Total lipids were isolated from skin samples using sequential extractions with different solvent mixtures according to a previously described procedure (45).…”