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分泌型卷曲相关蛋白4及其在癌症与细胞凋亡中的意义。

Secreted frizzled-related protein 4 and its implications in cancer and apoptosis.

作者信息

Pohl Sebastian, Scott Ross, Arfuso Frank, Perumal Vanathi, Dharmarajan Arun

机构信息

School of Biomedical Science, Faculty of Health Sciences, Curtin University, GPO Box U1987, Perth, Western Australia, 6845, Australia,

出版信息

Tumour Biol. 2015 Jan;36(1):143-52. doi: 10.1007/s13277-014-2956-z. Epub 2014 Dec 13.

Abstract

Secreted frizzled-related protein 4 (SFRP4) is a glycoprotein that acts as an antagonist of Wnt ligands, causing inhibition of the canonical Wnt signalling pathway. First noticed due to high expression levels during times of increased apoptosis, SFRP4 has been implicated in cell proliferation and differentiation and plays an important role in carcinogenesis. Many tumours such as endometrial, cervical, ovarian, prostate, bladder, colorectal, mesothelioma, pancreatic, renal, and oesophageal tumours are characterised by aberrant promoter hypermethylation, which causes variations in the expression level of SFRP4 when compared to normal cells. Combined experimental data appear to confirm the suggested role of SFRP4 as a local initiator of apoptosis; however, increased SFRP4 expression may not always correlate with an increase in apoptosis, possibly due to the complex interactions between different signalling pathways. SFRP4 can be explored for its use in novel therapeutic modalities as well as being a potential diagnostic biomarker.

摘要

分泌型卷曲相关蛋白4(SFRP4)是一种糖蛋白,作为Wnt配体的拮抗剂,可抑制经典Wnt信号通路。SFRP4最初因在细胞凋亡增加时表达水平升高而被发现,它与细胞增殖和分化有关,在肿瘤发生中起重要作用。许多肿瘤,如子宫内膜癌、宫颈癌、卵巢癌、前列腺癌、膀胱癌、结直肠癌、间皮瘤、胰腺癌、肾癌和食管癌,其特征是启动子异常高甲基化,与正常细胞相比,这会导致SFRP4表达水平发生变化。综合实验数据似乎证实了SFRP4作为局部凋亡启动子的作用;然而,SFRP4表达增加可能并不总是与细胞凋亡增加相关,这可能是由于不同信号通路之间复杂的相互作用。SFRP4可用于新型治疗模式,也是一种潜在的诊断生物标志物。

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