Survivin is not only a death encounter but also a survival protein for invading tumor cells.
Cell proliferation and cell death pathways meet at a pivotal crossroad, crucial to maintain normal homeostasis and to eliminate dangerous cells before they start dividing. Survivin (SVV) is an intriguing and fascinating protein at this crossroad that interfaces life and death, through its dual role in facilitating cell division and encountering apoptosis. SVV's prominent expression in essentially all human malignancies, and low or no expression in most normal tissues, suggests that it would be an ideal target for cancer-directed therapy. However, SVV has been recently described as a target for fine tuning by alternative splicing mechanism generating five defined splice variants and a number of other uncharacterized/bizarre isoforms. This diversity indicates that SVV, in addition to its known functions in tumorgenesis, angiogenesis and cardiovascular diseases, might be associated with other unknown functions. Intriguingly, new accumulating evidence from our own work and others, suggest a novel role for SVV in the mechanisms of tumor invasion and metastasis. The SVV pathway has now provided tangible opportunities for targeted, rational cancer therapy. It is therefore an attractive and promising therapeutic target not only for cancer but also for other diseases. Although a number of studies utilizing SVV as an anti-cancer strategy are well underway, further investigation into the exact molecular interactions underpinning its functions is critical for the success of such trials. Impeding development of safe and effective SVV antagonists for clinical use is due to a lack of understanding the molecular mechanisms by which SVV differentially affects apoptosis and cell division in both normal and malignant cells. In this report, in addition to reviewing the SVV known functions, we discuss the newly proposed mechanisms by which SVV might serve as a survival tool for invading tumor cells.
Ouhtit
Allal
A
Department of Pathology, Stanley S. Scott Cancer Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. aouhti@lsuhsc.edu
Matrougui
Khalid
K
Bengrine
Abderrahmane
A
Koochekpour
Shahriar
S
Zerfaoui
Mourad
M
Yousief
Zakaria
Z
D017209:Apoptosis; D002453:Cell Cycle; D002470:Cell Survival; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin