Baharudin Rashidah, Tieng Francis Yew Fu, Lee Learn-Han, Ab Mutalib Nurul Syakima
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya 47500, Malaysia.
Cancers (Basel). 2020 Feb 14;12(2):445. doi: 10.3390/cancers12020445.
Secreted frizzled-related protein 1 (SFRP1) is a gene that belongs to the secreted glycoprotein SFRP family. has been classified as a tumor suppressor gene due to the loss of expression in various human cancers, which is mainly attributed by epigenetic inactivation via DNA methylation or transcriptional silencing by microRNAs. Epigenetic silencing of may cause dysregulation of cell proliferation, migration, and invasion, which lead to cancer cells formation, disease progression, poor prognosis, and treatment resistance. Hence, restoration of expression via demethylating drugs or over-expression experiments opens the possibility for new cancer therapy approach. While the role of as a tumor suppressor gene is well-established, some studies also reported the possible oncogenic properties of in cancers. In this review, we discussed in great detail the dual roles of in cancers-as tumor suppressor and tumor promoter. The epigenetic regulation of expression will also be underscored with additional emphasis on the potentials of in modulating responses toward chemotherapeutic and epigenetic-modifying drugs, which may encourage the development of novel drugs for cancer treatment. We also present findings from clinical trials and patents involving to illustrate its clinical utility, extensiveness of each research area, and progression toward commercialization. Lastly, this review provides directions for future research to advance as a promising cancer biomarker.
分泌型卷曲相关蛋白1(SFRP1)是一种属于分泌型糖蛋白SFRP家族的基因。由于在多种人类癌症中表达缺失,它已被归类为肿瘤抑制基因,这主要归因于通过DNA甲基化的表观遗传失活或微小RNA介导的转录沉默。SFRP1的表观遗传沉默可能导致细胞增殖、迁移和侵袭的失调,进而导致癌细胞形成、疾病进展、预后不良和治疗耐药性。因此,通过去甲基化药物或过表达实验恢复SFRP1的表达为新的癌症治疗方法开辟了可能性。虽然SFRP1作为肿瘤抑制基因的作用已得到充分证实,但一些研究也报道了其在癌症中可能具有的致癌特性。在本综述中,我们详细讨论了SFRP1在癌症中的双重作用——作为肿瘤抑制因子和肿瘤促进因子。还将强调SFRP1表达的表观遗传调控,并特别关注其在调节对化疗药物和表观遗传修饰药物反应方面的潜力,这可能会促进新型癌症治疗药物的开发。我们还展示了涉及SFRP1的临床试验和专利的结果,以说明其临床应用价值、每个研究领域的广泛性以及商业化进程。最后,本综述为未来将SFRP1发展成为有前景的癌症生物标志物的研究提供了方向。