Marco Arese, Ph.D.
Associate Professor of Biochemistry University of Torino, School of Medicine
Neuroligin: a novel modulator of cell transformation and cancer diffusion through nerves.
Neuroligin (NLGN) is a neuronal and tumoral adhesion protein. Tumor-nerve interactions are a clinically significant, but often underestimated way of cancer diffusion, including colorectal cancer (CRC). Tumor and nerve relations occour through Perineural Invasion (PNI), namely the invasion of nearby nerves by cancer cells, and neo-neurogenesis, or the stimulation of neurite outgrowth by cancer through soluble signals. These aspects represent different conditions of a wide range of molecular interactions that are nevertheless poorly defined. There is no specific therapy able to target tumor nerve interactions. Therefore, new molecular players and therapies are needed.
This laboratory has been working on the extra-neuronal activities of NLGN for the last ten years. Since 2013 we have focused on the following questions on the role of tumoral/nervous NLGN (mainly in CRC): (a) How does it impact tumor “autonomous” cell behaviour? (b) Does it modulate PNI and neo-neurogenesis? The results obtained to date show that NLGN inhibits tumor cell proliferation, anchorage-independent growth and in vivo tumor growth but, conversely, promotes PNI.
Conclusions and perspectives:
If broadly confirmed, our data reveal NLGN as a double-faced cue (i.e. growth suppressing but pro- invasive). We now want to exploit the knowledge coming from the neuronal field, the large amount of reagents accumulated in this laboratory, and both in vitro and in vivo experimental settings (mouse xeno- and ortho- transplants) in order to fully answer the questions stated above.