S100A4 (MTS1) calcium binding protein in cancer growth, invasion and metastasis.
S100A4 (MTS1) calcium binding protein in cancer growth, invasion and metastasis.
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发表时间：
1998-07
影响因子：
2
通讯作者：
G. Sherbet;M. S. Lakshmi
中科院分区：
文献类型：
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作者：
G. Sherbet;M. S. Lakshmi
S100家族的钙结合蛋白已被证明参与多种生理功能，如细胞增殖、细胞外信号转导、细胞间粘附、运动以及癌症转移。S100基因家族的成员，即S100 A4（也称为mts 1、18 A2/mts 1、pEL-98、p9 Ka、p53）在控制细胞增殖以及在癌症侵袭和转移中所起的作用现在已经在许多实验室中被广泛研究。目前已知S100 A4基因编码的蛋白能够调节细胞周期进程，调节细胞间粘附以及癌细胞的侵袭和转移特性。S100 A4蛋白似乎能够隔离和禁用控制细胞G1-S转变的p53抑制蛋白，并且细胞从S期退出进入有丝分裂G2-M转变被认为涉及Stathmin（Op 18）基因表达的诱导。已发现该基因的表达与S100 A4的表达平行，S100 A4似乎也参与生长的稳态，还明显参与生长因子信号转导和凋亡性细胞死亡。有相当多的证据表明，S100 A4表达改变细胞的粘附特性，可能是通过重塑细胞外基质和促进细胞外基质中发生的粘附介导大分子的重新部署。使用转染技术，已经显示S100 A4的过表达增强癌细胞的肺定殖。相反，反义构建体的转染和表达抑制肺中的转移定位。血清和肿瘤组织中的S100蛋白水平越来越多地被监测，并被视为癌症进展状态的良好指标。关于S100 A4在人类黑色素瘤中的表达已经积累了有价值的证据。在乳腺癌中，已经发现S100 A4的表达水平与癌向区域淋巴结的转移扩散密切相关。本综述的目的是强调需要集中在S100蛋白一般和S100 A4特别是subserve目前归因于他们的各种功能的机制。
The S100 family of calcium binding proteins has been shown to be involved in a variety of physiological function, such as cell proliferation, extracellular signal transduction, intercellular adhesion, motility as well as cancer metastasis. The role played by a member of the S100 gene family, viz. S100A4 (also referred to as mtsl, 18A2/mtsl, pEL-98, p9Ka, metastasin) in the control of cell proliferation as well as in cancer invasion and metastasis has now been extensively studied in a number of laboratories. The protein encoded by S100A4 gene is now known to be capable of regulating cell cycle progression, modulating intercellular adhesion and invasive and metastatic properties of cancer cells. The S100A4 protein appears to be able to sequester and disable the p53 suppressor protein which controls G1-S transition of cells as well as the exit of cells from the S phase into mitosis G2-M transition is believed to involve the induction of stathmin (Op18) gene expression. The expression of this gene has been found to parallel that of S100A4, S100A4 also appears to take part in the homeostasis of growth, with apparent involvement also in growth factor signal transduction and apoptotic cell death. There is considerable evidence that S100A4 expression alters the adhesive properties of cells, possibly by remodelling the extracellular matrix and promoting a redeployment of adhesion-mediating macromolecules occurring in the extracellular matrix. Using transfection technology, it has been shown that over-expression of S100A4 enhances lung colonisation by cancer cells. The transfection and expression of antisense constructs, in contrast, inhibit metastatic localisation in the lung. S100 proteins levels in serum and in tumour tissue are increasingly being monitored and have been regarded as good indicators of the state of cancer progression. Valuable evidence has accumulated regarding the expression of S100A4 in human melanomas. In carcinoma of the breast, the level of expression of S100A4 has been found to be closely related to metastatic spread of the cancer to regional lymph nodes. The purpose of this review is to emphasise the need to focus sharply upon the mechanisms by which S100 proteins in general and S100A4 in particular subserve the wide variety of functions currently attributable to them.