An interlocker concept of carcinogenesis.

ED06-01

A critical feature in the sequence of events occurring during carcinogenesis is the development of irreversibility. The term "Interlocker" is used to denote a process by which irreversibility is brought about. Two of these processes are described below. The first concept is built around the occurrence of several common features found in cancers of solid organs. These include a loss of control of cell proliferation, disorganization, and infiltration. The concept is that the Interlocker is like a collar which binds together these common features irreversibly into a whole entity. It becomes fully active at the transition of precancer to cancer. The concept is highly attractive but information as to the nature of the collar is deficient. One possibility which has been suggested is that an Interlocker involves aberrant glycoproteins (Wattenberg, L.W. An Interlocker Concept of Carcinogenesis. Cancer Epidemiology, Biomarkers & Prevention 2006; 15:1425-1426). A second concept of an Interlocker is quite different. Central to this concept is the recognition that a critical feature of cancer is disorganization. An important manifestation of this disorganization is loss of cell/cell adhesions. A striking finding in this regard is the loss of E-cadherin cell/cell adhesions. Its loss has been shown to occur in carcinogenesis in a large number of tissues. The existence of an Interlocker would be important for a number of reasons. For cancer prevention it could provide a target for intervention, and one existing until a late point in the progression of precancer to cancer. For a collar type of Interlocker an agent that would break the collar could convert the lesion from being irreversible to being reversible, at least early in cancer. Finally the conceptualization of the existence of Interlockers itself is of value in providing new areas of research and new ways of evaluating data.