Cancer cells show profoundly altered mitotic divisions, and mitotic proteins are viewed as potential targets of novel antineoplastic drugs. Here, we have developed an in silico virtual screening to identify one small molecule targeting the interaction surface between microtubules and the kinetochore protein Hec1, thereby blocking microtubule dynamics. This small molecule effectively inhibits neoplastic growth, both in cultured cancer cells and in murine xenograft models, by promoting mitotic catastrophe and apoptotic cell death. This renders the molecule an interesting candidate for pre-clinical and clinical studies. On the whole, this study demonstrates that proteins controlling the dynamics of the kinetochore-microtubule interaction are important targets for the development of antineoplastic drugs.
Small molecules targeted to the microtubule-Hec1 interaction inhibit cancer cell growth through microtubule stabilization. Ferrara M, Sessa G, Fiore M, Bernard F, Asteriti IA, Cundari E, Colotti G, Ferla S, Desideri M, Buglioni S, Trisciuoglio D, Del Bufalo D, Brancale A, Degrassi F. Oncogene. 2017. doi: 10.1038/onc.2017.320. [Epub ahead of print]