文章：

人体组织嗜钾酶在癌症中的新作用

The emerging roles of human tissue kallikreins in cancer

原文发布日期：2004-11-01

DOI: 10.1038/nrc1474

类型: Review Article

开放获取: 否

要点：

1. Human tissue kallikreins (hKs) comprise a subgroup of 15 homologous secreted trypsin or chymotrypsin-like serine proteases, encoded by a tightly clustered multigene family on chromosome 19q13.4.
2. KLK transcription is modulated by an assortment of stimulatory and inhibitory factors, among which steroid hormones are the best characterized. The proteolytic activity of hKs is regulated in several ways, including zymogen activation; complex formation with endogenous plasma and/or tissue inhibitors, such as α₂-macroglobulin and serpins; inhibition by inorganic ions; and inactivation through internal (auto)fragmentation.
3. hKs are primarily expressed within the glandular epithelia of many organs and implicated in a range of normal physiological functions. New proteomic technologies could facilitate the identification of putative in vivo substrates and/or the substrate specificity for many of the newer, relatively uncharacterized hKs.
4. Kallikrein genes/proteins are aberrantly expressed in many cancer types and their expression is often associated with patient prognosis.
5. So far, experimental evidence indicates that hKs might promote or inhibit cancer-cell growth, angiogenesis, invasion and metastasis by proteolytic processing of growth-factor-binding proteins, activation of growth factors and other proteases, release of angiogenic or anti-angiogenic factors, and degradation of extracellular-matrix components. hKs are also implicated in the development of osteoblastic bone metastasis in prostate cancer.
6. The initial claim to fame of hKs is mainly attributed to the clinical impact of prostate-specific antigen as a biomarker for screening, diagnosis, staging and monitoring of prostate cancer. Recent reports indicate that many other kallikrein genes/proteins might prove to be promising tissue and/or serological cancer markers.
7. Exploitation and modulation of hK protease activity are attractive therapeutic approaches. hKs have been used in the activation of prodrugs and in the development of cancer vaccines, whereas hK promoters have been used for the specific delivery of toxic genes to tumour cells. Highly specific inhibitors of hK activity have also been developed and might represent promising agents for cancer treatment.

要点翻译：

1. 人组织激肽释放酶（hKs）包含15种同源性分泌型胰蛋白酶或糜蛋白酶样丝氨酸蛋白酶，它们由一个紧密聚集在19号染色体q13.4区域的多基因家族编码。
2. KLK基因的转录受多种刺激性和抑制性因子调控，其中甾体激素的特征最为明确。hKs的蛋白水解活性通过多种方式调节，包括酶原激活；与内源性血浆和/或组织抑制剂（如α2-巨球蛋白和丝氨酸蛋白酶抑制剂）形成复合物；无机离子抑制；以及通过内部（自身）片段化失活。
3. hKs主要在许多器官的腺体上皮中表达，并参与一系列正常生理功能。新的蛋白质组学技术有助于鉴定许多较新、特征相对不明的hKs的推定体内底物和/或底物特异性。
4. 激肽释放酶基因/蛋白在多种癌症类型中异常表达，其表达常与患者预后相关。
5. 迄今为止，实验证据表明hKs可能通过以下机制促进或抑制癌细胞生长、血管生成、侵袭和转移：蛋白水解处理生长因子结合蛋白、激活生长因子和其他蛋白酶、释放促血管生成或抗血管生成因子、以及降解细胞外基质成分。hKs还与前列腺癌成骨细胞性骨转移的发展有关。
6. hKs最初成名主要归功于前列腺特异性抗原作为生物标志物在前列腺癌筛查、诊断、分期和监测中的临床影响。近期报道表明，许多其他激肽释放酶基因/蛋白可能成为有前景的组织和/或血清学癌症标志物。
7. 利用和调节hK蛋白酶活性是颇具吸引力的治疗策略。hKs已被用于前体药物激活和癌症疫苗开发，而hK启动子则被用于将毒性基因特异性递送至肿瘤细胞。高特异性的hK活性抑制剂也已开发出来，可能成为有潜力的癌症治疗剂。

英文摘要：

Human tissue kallikreins (hKs), which are encoded by the largest contiguous cluster of protease genes in the human genome, are secreted serine proteases with diverse expression patterns and physiological roles. Although primarily known for their clinical applicability as cancer biomarkers, recent evidence implicates hKs in many cancer-related processes, including cell-growth regulation, angiogenesis, invasion and metastasis. They have been shown to promote or inhibit neoplastic progression, acting individually and/or in cascades with other hKs and proteases, and might represent attractive targets for therapeutic intervention.

摘要翻译： 

人类组织激肽释放酶（hKs）由人类基因组中最大的连续蛋白酶基因簇编码，是一类具有多种表达模式和生理功能的分泌型丝氨酸蛋白酶。尽管它们主要作为癌症生物标志物在临床上应用，但最新研究表明，hKs 参与了多种癌症相关过程，包括细胞生长调控、血管生成、侵袭和转移。它们可通过单独或与其他 hKs 及蛋白酶级联作用，促进或抑制肿瘤进展，并可能成为有吸引力的治疗干预靶点。

原文链接：

The emerging roles of human tissue kallikreins in cancer