Cathepsin B and its role(s) in cancer progression
Cathepsin B and its role(s) in cancer progression
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DOI：
10.1042/bss0700263
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Sloane, BF
中科院分区：
文献类型：
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作者：
Podgorski, I;Sloane, BF
实验和临床证据表明组织蛋白酶B与肿瘤侵袭和转移有关。在许多人类癌症中，组织蛋白酶B在mRNA、蛋白和活性水平上表达增加。此外，组织蛋白酶B在癌前病变中经常过度表达，这一观察结果将这种蛋白酶与局部浸润性癌症阶段联系起来。组织蛋白酶B在原发性癌症中表达增加，尤其是在肿瘤前病变中，表明该酶可能具有促凋亡的特征。组织蛋白酶B的表达在许多不同的水平上受到调节，从基因扩增，使用替代启动子，增加转录和替代剪接，到增加转录物的稳定性和可翻译性。在向恶性肿瘤转变的过程中，组织蛋白酶B的定位发生了变化，这可以通过在细胞外围和极化细胞的基极存在含组织蛋白酶B的囊泡来证明。由于组织蛋白酶B的表达增加和细胞内运输的变化，观察到肿瘤中组织蛋白酶B原的分泌增加。活性组织蛋白酶B也从肿瘤分泌，这一机制可能与溶酶体胞外分泌或表面激活剂的细胞外加工有关。组织蛋白酶B定位于肿瘤表面的小泡，在那里与膜联蛋白II异源四聚体结合。细胞表面组织蛋白酶B的激活导致下游蛋白水解级联的调节。
Experimental and clinical evidence has linked cathepsin B with tumour invasion and metastasis. Cathepsin B expression is increased in many human cancers at the mRNA, protein and activity levels. In addition, cathepsin B is frequently overexpressed in premalignant lesions, an observation that associates this protease with local invasive stages of cancer. Increased expression of cathepsin B in primary cancers, and especially in preneoplastic lesions, suggests that this enzyme might have pro-apoptotic features. Expression of cathepsin B is regulated at many different levels, from gene amplification, use of alternative promoters, increased transcription and alternative splicing, to increased stability and translatability of transcripts. During the transition to malignancy, a change in the localization of cathepsin B occurs, as demonstrated by the presence of cathepsin B-containing vesicles at the cell periphery and at the basal pole of polarized cells. Due to increased expression of cathepsin B and changes in intracellular trafficking, increased secretion of procathepsin B from tumours is observed. Active cathepsin B is also secreted from tumours, a mechanism likely to be facilitated by lysosomal exocytosis or extracellular processing by surface activators. Cathepsin B is localized to caveolae on the tumour surface, where binding to the annexin II heterotetramer occurs. Activation of cathepsin B on the cell surface leads to the regulation of downstream proteolytic cascade(s).