A new research article from Marco Trerotola’s group originated from a scientific collaboration involving various research groups of the G. D’Annunzio University, as well as national and international scientists has recently been published in Oncogene.

The study demonstrates that the receptor Trop-2 is a central hub for the assembly of a macromolecular signaling complex, that comprises transmembrane glycoproteins (including CD9, Na⁺/K⁺ ATPase, E-cadherin, ADAM10) and cytoplasmic effectors (including PKCa, cofilin-1, b-actin, myosin, a-actinin, annexins). This complex is induced to boost cancer cell growth and invasion by Trop-2 clustering at the cell membrane, and acts through a feed-forward mechanism from transduction of Ca²⁺ signals and processing of E-cadherin at the cell membrane to phosphorylation events involving cytoplasmic signaling effectors and ultimately converging on the stimulation of Akt and ERK pathways.

Novel key technologies such as the targeted inhibition of CD9 expression through CRISPR/Cas9-dependent gene editing allowed to define a critical contribution of this protein in the Trop-2 signaling network, both in 2D/3D settings in vitro and in tumor xenografts in vivo.

Finally, overexpression of the components of this Trop-2-driven super-complex were found to significantly worsen disease-free and overall survival of patients with colorectal cancer, supporting a pivotal relevance of these findings in malignant progression.

Link to the Article : https://www.nature.com/articles/s41388-022-02220-1

Trop-2, Na⁺/K⁺ ATPase, CD9, PKCα, cofilin assemble a membrane signaling super-complex that drives colorectal cancer growth and invasion

Guerra E., Relli V., Ceci M., Tripaldi R., Simeone P., Aloisi AL., Pantalone L., La Sorda R., Lattanzio R., Sacchetti A., Havas K., Guarnieri S., Vergara D., Fournier I., Salzet M., Tinari N., Piantelli M., Trerotola M.* and Alberti S.*, Oncogene (7 Feb 2022)

* co-last and co-corresponding authors