Transcriptional Regulation of Survivin: New Target for Cancer Treatment

Survivin is a unique member of the IAP family. It plays dual roles in inhibiting apoptosis and in regulating mitosis. Moreover, it is highly expressed in almost all types of human cancer but undetected in most normal adult tissues. High levels of survivin expression have been associated with cancer progression, drug resistance, poor prognosis and short patient survival. Therefore, survivin is regarded as a promising target for cancer treatment. Modulation of survivin expression may constitute an important, specific therapeutic approach. This review briefly summarizes the cellular signaling that regulates survivin transcription and evidence that upregulation of survivin expression promotes anticancer resistance and tumor progression. Recent studies demonstrate that the survivin promoter is strongly activated by several transcription factors including Sp/KLF family members and the β-catenin/TCF signaling pathway, which positively regulate cell proliferation and mediate cell survival, transformation, and tumorigenesis. Activation of survivin by these transcription factors is usually associated with mutation of tumor suppressor genes such as p53 and APC. Thus, this review will focus on the roles of transcription factors and their interactions with tumor suppressor genes in regulating survivin expression, and targeting of survivin promoter and transcriptional regulation, to assess whether that targeting might be a viable therapeutic approach against cancer.