Investigations of survivin: the past, present and future

Abstract

Survivin is a member of the inhibitors-of-apoptosis protein (IAPs) family. It promotes cell survival through interference with multiple cell cycle-related proteins such as INCENP and Aurora B kinase. Survivin also inhibits cell death through interference with both caspase-dependent and -independent cell apoptosis. Interestingly, recent evidence suggests that survivin may also play a role in the regulation of cancer cell autophagy. At the clinical level, studies on clinical specimens have shown that survivin expression is up-regulated in various human cancers and its up-regulation is associated with tumour resistance to both chemotherapy and radiation therapy. On the basis of these findings, survivin has been proposed as an attractive target for new anti-cancer interventions. However, despite the role that survivin plays in cancer cell survival and anti-drug response, the development of survivin inhibitors is relatively slow as compared to other therapeutic inhibitors for cancer treatment. In this review, the relationships between survivin expression and the causation of drug resistance in cancers are re-addressed. This review also summarizes the recent development of survivin inhibitors for clinical usage.

Survivin: a new player during erythroblast maturation

“…13 In addition to its function as an apoptosis inhibitor, survivin is a chromosomal passenger protein that mediates spindle assembly checkpoint and cytokinesis. [14][15][16][17][18][19] In addition to normal proliferating cells, survivin is also frequently over-expressed in cancer cells where it likely also serves as an inhibitor of apoptosis. [14][15][16][17][18][19] As such, survivin has been proposed as an attractive target for anticancer therapies and, in some cases, has even been proposed as a cancer-specific gene.…”

“…[14][15][16][17][18][19] In addition to normal proliferating cells, survivin is also frequently over-expressed in cancer cells where it likely also serves as an inhibitor of apoptosis. [14][15][16][17][18][19] As such, survivin has been proposed as an attractive target for anticancer therapies and, in some cases, has even been proposed as a cancer-specific gene. Survivin plays an essential role in cell division as a component of the chromosome passenger complex (CPC), which is comprised of survivin, aurora B kinase, INCENP (inner centromere protein) and borealin.…”

Assessment of mRNA Splice Variants by qRT-PCR

“…Survivin, a protein highly expressed in human cancers, is associated with chemotherapy resistance [1–5]. Survivin plays a dual intracellular role as an antiapoptotic protein and as a regulator of mitosis [1, 6].…”

“…Survivin plays a dual intracellular role as an antiapoptotic protein and as a regulator of mitosis [1, 6]. Alternative splicing of the human survivin gene ( BIRC5 ) generates five splice variants, including wild-type (WT) survivin (142 aa), survivin 2α (74 aa), survivin 2B (165 aa), survivin ΔEx3 (137 aa), and survivin 3B (120 aa) ( see Fig.…”

“…1) [7–10]. The expression levels and the subcellular localization patterns of each survivin isoform have been shown to be associated with their functional properties [1, 7, 11, 12]. For example, it has been reported that, compared with their taxane-sensitive counterparts, taxane-resistant ovarian cancer cells express higher survivin 2B messenger RNA (mRNA) levels [13].…”