ID proteins in tumour initiation and progression

Abstract

Despite decades of cancer research, the search for key oncogenesis regulators as potential targets for novel therapies continues. Proteins, belonging to ID family, may be such promising candidates. They are DNA binding inhibitors, mainly of the bHLH transcription factor subfamily, which regulate genes related to cell differentiation. ID genes are normally expressed in progenitor and stem cells inhibiting their differentiation. Nevertheless, in some cases the expression of ID genes was observed to direct cell maturation process. In tumors ID proteins manifest hallmarks of both oncogenes and tumor suppressors, depending on the affected organ. As a consequence of deregulated signaling pathways occurring in cancers, ID genes may be overexpressed or silenced. In effect, abnormal levels of ID proteins invariably lead to dedifferentiation of cancer cells and give them the characteristics of stem cells, such as the ability for self-renewal, avoidance of apoptosis and senescence. Moreover, ID proteins take part in metastasis and angiogenesis. The involvement of ID proteins in carcinogenesis encourages to further investigate their mechanisms of action and implement this knowledge in the design of new drugs.