Trop-2 governs anti-metastatic desmosomal integrity

Trop-2 and DSG2 are proteins critical for the formation of intercellular contacts in healthy epithelial tissue. In cancer cells, their roles have been reported to vary, acting as either tumor suppressors or promoters depending on the context. In our study, deletion of Trop-2 or DSG2 in T-47D breast cancer cell lines resulted in a similar phenotype. In vivo, xenografts derived from these knockout cell lines exhibited an increased ability to form distant metastases. The present study links the observed in vivo metastatic phenotype to transcriptomic alterations identified in both knockout cell lines and their corresponding xenografts. Overall design: We performed a differential gene expression analysis comparing control T-47D cells to Trop-2 and DSG2 knockout (KO) clones cultured in 2D in vitro. Next, we compared Trop-2 wild-type (WT) xenografts to DSG2 KO xenografts and Trop-2 KO xenografts to investigate transcriptomic changes in vivo.