The multiple roles of Id-1 in cancer progression.
Id-1 (Inhibitor of differentiation/DNA binding) is a member of the helix-loop-helix protein family expressed in actively proliferating cells. It regulates gene transcription by heterodimerization with the basic helix-loop-helix transcription factors and therefore inhibits them from DNA binding and transactivation of their target genes. Early studies showed that Id-1 functions mainly as a regulator in cellular differentiation of the muscle cells. The oncogenic role of Id-1 was revealed recently by the finding that Id-1 expression was able to induce cancer cell growth and promote cell survival. In addition, Id-1 protein was frequently overexpressed in over 20 types of cancer, supporting its role in the tumorigenesis of a wide range of tissues. However, the fact that Id-1 was able to activate multiple pathways involved in tumor progression suggests that Id-1 may in addition function in promotion of tumor development. For example, overexpression of Id-1 was found to induce expression of MT1-MMP protein, leading to invasion of breast cancer cells. A close association between Id-1 expression and angiogenesis has also been demonstrated recently in both normal and cancer cells. Accordingly, in prostate cancer cells, expression of Id-1 was able to activate EGF-R and nuclear factor-kappaB activities and resulted in progression to androgen independence. In addition, in both nasopharyngeal carcinoma and prostate cancer cells, Id-1 expression was found to protect the cells from chemotherapeutic drug-induced apoptosis through regulation of the Raf-1/MAPK and JNK pathways. This review will discuss recent evidence supporting the role of Id-1 in tumor progression and the mechanisms involved.
Ling
Ming-Tat
MT
Cancer Biology Group, Department of Anatomy, The University of Hong Kong, Hong Kong, China.
Wang
Xianghong
X
Zhang
Xiaomeng
X
Wong
Yong-Chuan
YC
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000628:therapy
D051798:Inhibitor of Differentiation Protein 1