Signaling together apart

Dormant tumors awaken hat happens during tumor remission? After chemotherapy, tumor cell numbers may be reduced, or surviving cells may enter an altered, dormant state. Evidence for dormancy now comes from Catherine Shachaf, Dean Felsher (Stanford University, Stanford, CA), and colleagues. In their mouse model, liver tumors can be forced into dormancy and then reawakened at will. As in previous studies, regression was induced by shutting off the oversupply of MYC, in this case using a tetracycline-controlled promoter. Trans-genic mice took ~12 weeks to develop the MYC-induced tumors, but within 4 days of MYC inactivation the cells died or differentiated into normal liver cells. Tumors regressed but could later be reactivated by switching MYC back on. The persistence of dormant tumor cells was demonstrated by transplanting tumor cells containing transgenes for both luciferase and the tetra-cycline-controlled MYC. Even when MYC was inactivated the luciferase signal persisted in the transplanted cells, which looked like normal liver cells. Turning MYC back on restored tumorigenesis, increasing cell number and thus luciferase activity. Reversible dormancy has not been seen in previous MYC inactivation studies. Felsher believes that the differences are explained by the properties of the tumors' originating tissues. Lacking MYC, tumor cells from a terminally differentiated tissue such as bone resort to terminal differentiation; those from the apoptotic-prone hematopoietic compartment die; and those from liver (a tissue that is rich in stem cells and can regenerate) differentiate but produce many stem cells. It is those stem cells that may perpetuate the dormant state and that Felsher wants to understand. fter being cleaved apart, two halves of a split personality receptor protein are free to wander far away from each other, say Kirill Volynski, Yuri Ushkaryov, and colleagues (Imperial College, London, UK). But when signaling is needed the two halves reunite. The receptor, called latrophilin, is known only as a binding site for the black widow poison latrotoxin. Although no endogenous ligand for latrophilin is known, a varied family of receptors exists with a similar organization. Each family member has two domains: an NH 2-terminal fragment (NTF) that interacts with other cell surface or possibly extracellular matrix proteins, and a COOH-terminal fragment (CTF) that resembles a G-protein–coupled receptor (GPCR). The two domains were known to be cleaved, but the persistence of the NTF on the cell surface led previous workers to assume that the transmembrane-less NTF must remain bound to CTF. The London group …