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一条导致前列腺癌细胞恶性进展的新型皮肤脂肪酸结合蛋白相关信号通路。

A novel cutaneous Fatty Acid-binding protein-related signaling pathway leading to malignant progression in prostate cancer cells.

作者信息

Bao Zhengzheng, Malki Mohammad I, Forootan Shiva S, Adamson Janet, Forootan Farzad S, Chen Danqing, Foster Christopher S, Rudland Philip S, Ke Youqiang

机构信息

Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, the University of Liverpool, Liverpool, UK.

出版信息

Genes Cancer. 2013 Jul;4(7-8):297-314. doi: 10.1177/1947601913499155.

Abstract

Cutaneous fatty acid-binding protein (C-FABP), a cancer promoter and metastasis inducer, is overexpressed in the majority of prostatic carcinomas. Investigation of molecular mechanisms involved in tumor-promoting activity of C-FABP has established that there is a fatty acid-initiated signaling pathway leading to malignant progression of prostatic cancer cells. Increased C-FABP expression plays an important role in this novel signaling pathway. Thus, when C-FABP expression is increased, excessive amounts of fatty acids are transported into the nucleus where they act as signaling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ). The activated PPARγ then modulates the expression of its downstream target regulatory genes, which eventually lead to enhanced tumor expansion and aggressiveness caused by an overgrowth of cells with reduced apoptosis and an increased angiogenesis.

摘要

皮肤脂肪酸结合蛋白(C-FABP)是一种癌症促进因子和转移诱导因子,在大多数前列腺癌中过度表达。对C-FABP促肿瘤活性相关分子机制的研究表明,存在一条由脂肪酸启动的信号通路,导致前列腺癌细胞发生恶性进展。C-FABP表达增加在这条新的信号通路中起重要作用。因此,当C-FABP表达增加时,过量的脂肪酸被转运到细胞核中,在那里它们作为信号分子刺激其核受体过氧化物酶体增殖物激活受体γ(PPARγ)。激活的PPARγ随后调节其下游靶调控基因的表达,最终导致肿瘤扩张增强和侵袭性增加,这是由于细胞过度生长、凋亡减少和血管生成增加所致。

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