The detergent-soluble cytoplasmic pool of survivin suppresses anoikis and its expression is associated with metastatic disease of human colon cancer.
The detergent-soluble cytoplasmic pool of survivin suppresses anoikis and its expression is associated with metastatic disease of human colon cancer.
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DOI：
10.1371/journal.pone.0055710
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tatsuka M
中科院分区：
文献类型：
--
作者：
Hori M;Miki T;Okamoto M;Yazama F;Konishi H;Kaneko H;Shimamoto F;Ota T;Temme A;Tatsuka M
生存素是染色体乘客复合体（CPC）的一个组成部分，对准确的染色体分离至关重要。干扰Survivin在有丝分裂中的功能可导致染色体分离错误和胞质分裂缺陷。Survivin含有杆状病毒IAP重复序列（BIR），因此最初被分类为凋亡抑制蛋白（IAP），但其在细胞应激后凋亡中的作用仍不清楚。我们在这里证明，生存素主要抑制失巢凋亡，一种形式的程序性细胞死亡诱导的细胞粘附细胞外基质的损失。有趣的是，异位过表达EGFP-Survivin的细胞在失去细胞-基质相互作用后显示IκB-α的表达减少。随后的亚细胞蛋白分级分离和免疫沉淀实验显示，XIAP与去污剂可溶性Survivin相互作用，已知其协同激活NF-κB信号传导。对结肠直肠癌细胞系和结肠直肠癌组织中去污剂可溶性Survivin的表达水平的检查显示，去污剂可溶性细胞质Survivin水平与结肠直肠癌中的失巢凋亡易感性呈负相关。因此，可溶性Survivin可能是结直肠癌淋巴结转移和远处转移的一个有前景的预测性生物标志物。我们的结论是洗涤剂可溶性Survivin在经历失巢凋亡的间期细胞中的抗凋亡功能至少通过XIAP/IκB-α/NF-κB信号转导介导。
Survivin is a component of the chromosomal passenger complex (CPC) that is essential for accurate chromosome segregation. Interfering with the function of Survivin in mitosis leads to chromosome segregation errors and defective cytokinesis. Survivin contains a Baculovirus IAP Repeat (BIR) and therefore was originally classified as inhibitor of apopotosis protein (IAP), yet its role in apoptosis after cellular stress remains largely unknown. We demonstrate here, that Survivin predominantly suppresses anoikis, a form of programmed cell death induced by loss of cellular adhesion to extracellular matrix. Interestingly, cells ectopically overexpressing EGFP-Survivin showed after loss of cell-matrix-interaction a decreased expression of IκB-α. Subsequent subcellular protein fractionation and immunoprecipitation experiments revealed that XIAP interacts with detergent-soluble Survivin which is known to cooperatively activate NF-κB signaling. Examination of the expression levels of detergent soluble Survivin in colorectal cancer cell lines and in colorectal cancerous tissues revealed that detergent soluble cytoplasmic Survivin levels correlated inversely with anoikis susceptibility in colorectal cancer. Therefore, the detergent soluble cytoplasmic Survivin might be a promising predictive biomarker for lymph node and distant metastases of colorectal cancer. We conclude that an anti-apoptotic function of detergent-soluble Survivin in interphase cells experiencing anoikis is mediated at least via XIAP/IκB-α/NF-κB signaling.
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DOI：
10.1042/bj20100814
发表时间：
2010-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Altieri DC
通讯作者：
Altieri DC
影响因子：
4.8
作者：
Jones, G;Jones, D;Chu, YX
通讯作者：
Chu, YX
影响因子：
15.9
作者：
Dohi, T;Beltrami, E;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
4
作者：
Kaur, Harpreet;Bekier, Mike E.;Taylor, William R.
通讯作者：
Taylor, William R.
影响因子：
3.4
作者：
Kawai, H;Kitamura, Y;Suzuki, F
通讯作者：
Suzuki, F