文章：

在人类癌症酪氨酸磷组中

Inside the human cancer tyrosine phosphatome

原文发布日期：2010-12-23

DOI: 10.1038/nrc2980

类型: Review Article

开放获取: 否

要点：

1. The protein tyrosine phosphatase (Ptp) family comprises 107 members that are classified into four classes on the basis of the amino acid sequences of their catalytic domains.
2. Recent evidence has shown that members of the Ptp family are key components of tumorigenesis in various human cancers, exerting either putative oncogenic or tumour suppressive functions, depending on the cellular context.
3. Genetic alterations such as mutation, deletion and amplification are the most important features for putative oncogenic PTPs, whereas in most cases epigenetic modifications such as DNA methylation counter the tumour suppressive functions of PTPs.
4. Recent advances have begun to decipher the molecular mechanisms by which putative oncogenic PTPs may drive tumorigenesis in human cells. Proliferation, survival, apoptosis, vesicular trafficking, adhesion, migration and invasion are all altered by the aberrant functions of PTPs during tumour development.
5. Evidence for an association between PTPs and an increased risk of developing cancer remains controversial and elusive. Here, we focus on the pertinent genetic and functional data that support the relevance of members of the Ptp family to human cancer.
6. PTP inhibitors are currently being developed. However, a better understanding of the basic biology of PTPs in human tumour development will be required to improve the therapeutic use of such inhibitors.

要点翻译：

1. 蛋白酪氨酸磷酸酶家族包含107个成员，根据其催化结构域的氨基酸序列可分为四大类。
2. 最新证据表明，该家族成员在不同人类癌症的肿瘤发生中扮演关键角色，根据细胞环境差异可发挥推定致癌或肿瘤抑制功能。
3. 基因改变（如突变、缺失和扩增）是推定致癌性PTPs最重要的特征，而在大多数情况下，表观遗传修饰（如DNA甲基化）会抵消PTPs的肿瘤抑制功能。
4. 近期研究进展开始揭示推定致癌性PTPs在人类细胞中驱动肿瘤发生的分子机制：增殖、存活、凋亡、囊泡运输、粘附、迁移和侵袭等过程均在肿瘤发展过程中因PTPs功能异常而发生改变。
5. 关于PTPs与癌症发病风险增加相关性的证据仍存在争议且难以明确。本文重点探讨支持PTP家族成员与人类癌症相关性的遗传学和功能学数据。
6. 目前PTP抑制剂正在研发中，但需要更深入理解PTPs在人类肿瘤发生中的基础生物学作用，才能优化此类抑制剂的治疗应用。

英文摘要：

Members of the protein tyrosine phosphatase (Ptp) family dephosphorylate target proteins and counter the activities of protein tyrosine kinases that are involved in cellular phosphorylation and signalling. As such, certain PTPs might be tumour suppressors. Indeed, PTPs play an important part in the inhibition or control of growth, but accumulating evidence indicates that some PTPs may exert oncogenic functions. Recent large-scale genetic analyses of various human tumours have highlighted the relevance of PTPs either as putative tumour suppressors or as candidate oncoproteins. Progress in understanding the regulation and function of PTPs has provided insights into which PTPs might be potential therapeutic targets in human cancer.

摘要翻译： 

蛋白酪氨酸磷酸酶（Ptp）家族成员可使靶蛋白去磷酸化，拮抗参与细胞磷酸化与信号转导的蛋白酪氨酸激酶的活性。因此，某些PTP可能具有抑癌作用。确实，PTP在抑制或调控生长方面发挥重要作用，但越来越多的证据表明，部分PTP也可能表现出促癌功能。近期对多种人类肿瘤的大规模遗传分析强调，PTP要么可能是潜在的抑癌基因，要么是候选的癌蛋白。对PTP调控与功能理解的进展，已为我们指明哪些PTP可能成为人类癌症的潜在治疗靶点。

原文链接：

Inside the human cancer tyrosine phosphatome