The Senescent Side of Tumor Suppression

Abstract

Neoplastic transformation of human cells is a rare event that requires overcoming anti-tumoral cellular responses. Oncogene-induced senescence (OIS) is considered a crucial tumor suppressor mechanism controlling unchecked proliferation driven by oncogenic mutation. However, the analysis of OIS has been restricted so far to cultured cells. Recently, we have identified novel molecular markers of OIS and we have demonstrated the occurrence of senescence using mouse models of oncogenic activation. Importantly, we have found that senescent cells are abundant in premalignant lesions of the skin, the lung, and the pancreas. In contrast, senescent cells were rare in the malignant lesions developed by these same animals. These observations, together with similar ones by other investigators, strongly argue for the occurrence of OIS in vivo and for its active role in restricting tumor development. These results open the possibility of using senescence markers as diagnostic and prognostic tools, and prompt the investigation on the potential therapeutical use of senescence-inducing drugs.