Surana Rohit, Sikka Sakshi, Cai Wanpei, Shin Eun Myoung, Warrier Sudha R, Tan Hong Jie Gabriel, Arfuso Frank, Fox Simon A, Dharmarajan Arun M, Kumar Alan Prem
Cancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
Biochim Biophys Acta. 2014 Jan;1845(1):53-65. doi: 10.1016/j.bbcan.2013.11.004. Epub 2013 Dec 5.
The Wnt (wingless-type) signaling pathway plays an important role in embryonic development, tissue homeostasis, and tumor progression becaluse of its effect on cell proliferation, migration, and differentiation. Secreted frizzled-related proteins (SFRPs) are extracellular inhibitors of Wnt signaling that act by binding directly to Wnt ligands or to Frizzled receptors. In recent years, aberrant expression of SFRPs has been reported to be associated with numerous cancers. As gene expression of SFRP members is often lost through promoter hypermethylation, inhibition of methylation through the use of epigenetic modifying agents could renew the expression of SFRP members and further antagonize deleterious Wnt signaling. Several reports have described epigenetic silencing of these Wnt signaling antagonists in various human cancers, suggesting their possible role as tumor suppressors. SFRP family members thus come across as potential tools in combating Wnt-driven tumorigenesis. However, little is known about SFRP family members and their role in different cancers. This review comprehensively covers all the available information on the role of SFRP molecules in various human cancers.
Wnt（无翅型）信号通路因其对细胞增殖、迁移和分化的影响，在胚胎发育、组织稳态和肿瘤进展中发挥着重要作用。分泌型卷曲相关蛋白（SFRPs）是Wnt信号的细胞外抑制剂，通过直接结合Wnt配体或卷曲受体发挥作用。近年来，有报道称SFRPs的异常表达与多种癌症相关。由于SFRP成员的基因表达常常因启动子高甲基化而缺失，使用表观遗传修饰剂抑制甲基化可以恢复SFRP成员的表达，并进一步拮抗有害的Wnt信号。一些报道描述了这些Wnt信号拮抗剂在各种人类癌症中的表观遗传沉默，表明它们可能作为肿瘤抑制因子发挥作用。因此，SFRP家族成员有望成为对抗Wnt驱动的肿瘤发生的潜在工具。然而，人们对SFRP家族成员及其在不同癌症中的作用知之甚少。本综述全面涵盖了关于SFRP分子在各种人类癌症中作用的所有现有信息。
