Proteolytic processing of the transmembrane receptor Trop-2 stimulates cancer progression.

This paper demonstrates that a proteolytic cleavage occurs in the extracellular domain of the transmembrane receptor Trop-2, and activates this molecule inducing human cancer progression.

Trop-2 is a transmembrane glycoprotein expressed in epithelial tissues and up-regulated in human cancer. No Trop-2 cleavage is detected in normal human tissues, whereas tumors (including skin, ovary, colon, and breast cancers) show extensive Trop-2 processing. Coimmunoprecipitation and mass spectrometry analysis revealed that ADAM10 physically interacts with Trop-2, and is a candidate effector protease of this molecule. Consistent with this, inhibition of ADAM10 by specific drugs and by RNA interference results in unprocessed Trop-2, which is unable to induce cancer progression in vitro and in vivo. Altogether, these data indicate that Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis.

Title: Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis

Authors: Marco Trerotola, Emanuela Guerra, Zeeshan Ali, Anna Laura Aloisi, Martina Ceci, Pasquale Simeone, Angela Acciarito, Paola Zanna, Giovanna Vacca, Antonella D’Amore, Khouloud Boujnah, Valeria Garbo, Antonino Moschella, Rossano Lattanzio and Saverio Alberti