Loss of hSef promotes metastasis through upregulation of EMT in prostate cancer

We have previously reported that the negative signaling regulator Similar Expression to FGF (hSef) is downregulated in prostate cancer and its loss is associated with clinical metastasis. Here, we explored the mechanistic basis of this finding. We first confirmed our clinical observation by testing hSef manipulation in an in vivo metastasis model. hSef stable expressing cells (PC3M‐hSef) or empty vector controls (PC3M‐EV) were injected subcutaneously into the lateral thoracic walls of NOD‐SCID gamma mice and lungs were harvested at autopsy. In this model, 6/7 PC3M‐EV xenografts had definitive lung micro‐metastasis whilst only 1/6 PC3M‐hSef xenografts exhibited metastasis recapitulating the clinical scenario (p = 0.03). Gene expression studies revealed key perturbations in genes involved in cell motility and epithelial to mesenchymal transition (EMT) along with alterations in cognate signaling pathways. These results were validated in an EMT specific PCR array whereby hSef over‐expression and silencing reciprocally altered E‐Cadherin expression (p =
What's new? The loss of negative signaling regulators may be implicated in prostate cancer metastasis, but the underlying mechanisms remain unclear. Here, by using a combination of xenograft, gene expression microarray, phosphokinase array and quantitative PCR techniques, the authors provide first evidence that the negative regulator hSef plays a key role in regulating epithelial to mesenchymal transition (EMT) in prostate cancer, which in turn results in changes in the metastatic ability of tumor cells. The results support the notion that the expression levels of hSef and other negative signaling regulators may be key biomarkers for the identification of triggers for metastasis.