Survivin, a member of the inhibitor of apoptosis (IAP) protein family that inhibits caspases and blocks cell death, is highly expressed in most cancers and is associated with a poor clinical outcome. Survivin has consistently been identified by molecular profiling analysis to be associated with high tumour grade cancers, different disease survival and recurrence. Polymorphisms in the survivin gene are emerging as powerful tools to study the biology of the disease and have the potential to be used in disease prognosis and diagnosis. The survivin gene polymorphisms have also been reported to influence tumour aggressiveness as well as survival of cancer patients.
An overview of survivin
The survivin gene is a member of the IAP family with the smallest relative molecular weight, located at chromosome 17q25, 14.7 kb in length. It contains 4 exons and 3 introns and encodes a protein of 142 amino acids with a molecular weight of 16, 500. And it is widely expressed in human embryonic tissues and most tumor tissues and has the biological function of inhibiting cell apoptosis and regulating cell mitosis, as well as, it is an important factor in contacting cell cycle and apoptosis.
Inhibition of survivin
The molecular companion HPS90 amino terminal can be combined with the amino acid sequence 7-lys90 of survivin, which is beneficial to the stable expression of survivin. HSP90 inhibitors, such as 17-AGG and Shepherdin , can reduce the survivin. For example, shepherdin can penetrate cells and binds between Hsp 90 and survivin, occupying the ATP binding sites, loosening the client protein, and activating the apoptotic pathway and non-apoptosis pathway to cause tumor cells death. In addition, Shepherdin does not affect the viability of normal cells and the cloning and formation of hematopoietic progenitor cells.
Survivin and diseases
High expression of survivin was detected in many solid tumors and hematopoietic malignancies, and the survival rate of the patients with positive expression was lower. And the recurrence rate was higher, closely related to the prognosis. High expression of survivin was also detected in a variety of tumor cell lines in vitro. The results of 60 tumor cell lines used by the National Cancer Research Center shows that Survivin is widely expressed in 60 kinds of tumor cell lines, including breast cancer, lung cancer, colon cancer, ovarian cancer, prostate cancer, kidney cancer, liver cancer, melanoma, leukemia, lymphoma, and so on, which has the highest expression in breast cancer and lung cancer, and the lowest expression of renal carcinoma.