Inhibition of Stathmin1 Accelerates the Metastatic Process
Menée in vitro, cette étude met en évidence le rôle joué par la protéine STMN1 dans le processus métastatique
The oncoprotein Stathmin 1 (STMN1) is upregulated in most, if not all, cancers of epithelial cell origin; therefore STMN1 is considered a target for cancer therapy. However its role during metastasis has not been investigated. Here we report for the first time that STMN1 strongly inhibits metastatic behavior in both normal epithelial and cancerous epithelial cells. Initially, loss-of-STMN1 compromises cell-cell adhesion. This is followed by epithelial-to-mesenchymal-like transition (EMT), increased cell migration, and metastasis via cooperative activation of p38 and through TGF-β-independent and dependent mechanisms. In contrast, expressing STMN1 restores cell-cell adhesion and reverses the metastatic cascade. Primary prostate epithelial cell cultures from benign to undifferentiated adenocarcinoma clinical biopsies demonstrate that EMT-like cells arise while the cancer is still organ-confined and that their emergence is tumor-stage specific. Furthermore, primary EMT-like cells exhibit metastatic behavior both in vitro and in vivo as compared to their non-EMT counterpart. These observations predict that using STMN1 as a generic therapeutic target might accelerate metastasis. Instead, there may be a tumor stage-specific "window-of-opportunity" in which conserving STMN1 expression is required to inhibit emergence of metastatic disease.
Cancer Research 2012