HMGA2 is a Driver of Tumor Metastasis
Mené à l'aide d'un modèle murin, cette étude met en évidence le rôle joué par la protéine HMGA2 dans le processus métastatique d'un cancer du sein
The non-histone chromatin binding protein HMGA2 is expressed predominantly in the mesenchyme prior to its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression of HMGA2 in epithelial cells induces epithelial-mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known regarding in vivo modulation of HMGA2 and its effector functions in tumor metastasis. Here we report that HMGA2 loss-of-function in a mouse model of cancer reduces tumor multiplicity. HMGA2-positive cells were identified at the invasive front of human and mouse tumors. Additionally, in a mouse allograft model, HMGA2 overexpression converted non-metastatic 4TO7 breast cancer cells to metastatic cells that homed specifically to liver. Interestingly, expression of HMGA2 enhanced TGFbeta; signaling by activating expression of the TGFbeta; type II receptor (TGFbetaRII), which also localized to the invasive front of tumors. Together our results argued that HMGA2 plays a critical role in EMT by activating the TGFbeta; signaling pathway, thereby inducing invasion and metastasis of human epithelial cancers.