[Nectin and nectin-like molecules as markers, actors and targets in cancer]. / Nectines et nectines-like : marqueurs, acteurs et cibles de l'oncogenèse.

Nectin and nectin-like (necl) proteins form a family of 9 adhesion molecules that belong to the immunoglobulin superfamily. They play a key role in different biological processes such as cell polarity, proliferation, differentiation and migration in epithelial, endothelial, immune and nervous systems. Besides their role in physiology, they have been involved in different pathological processes in humans. They serve as virus receptors (poliovirus and herpes simplex virus), they are involved in orofacial malformation (CLPED1) and recently they have been described as markers, actors and potential therapeutics targets in cancer. Among them, necl-5, nectin-2 and nectin-4 are overexpressed in tumors, and are associated with a poor prognosis. On the opposite, necl-1, necl-2 and necl-4 act as tumor suppressors and are repressed in cancer. The involvement of nectins and necls molecules in cancer and their potential used in therapy is discussed in this review.

The centrosomal FOP protein is required for cell cycle progression and survival.

FOP is a centrosomal protein originally discovered as a fusion partner of FGFR1 in patients with a rare stem cell myeloproliferative disorder. In DT40 chicken lymphocytes, we show that the normal FOP protein localizes at the centrosome throughout the cell cycle and preferentially accumulates at the distal end of the mother centriole. We used homologous recombination in DT40 cells to generate an inducible null mutant for FOP. Loss of FOP induces apoptosis in the G(1) phase of the cell cycle with accumulation of a 32 kDa P53 tumor suppressor isoform and NOXA and FAS transcripts. However, centrosome integrity and microtubule organization are conserved without FOP and mitotic division and cytokinesis are as efficient as in control cells. Our results suggest that FOP is involved in G(1) to S signaling and thus in proliferation/death fate. Several reports show that centrosome alteration can lead to an arrest in G(1) and, possibly, to senescence in a fraction of cells. The phenotype we observed is more severe in FOP null cells. This could be dependent on the cell context or on the efficiency of a knock out that allows the complete disappearance of the target protein and prevents any de novo synthesis. This is an important observation in regard to the current discussion of what consequence centrosome perturbation could have on a cell and shows that a centrosomal protein can be necessary for cell cycle progression and survival.