Naeem Abdulghani A, Abdulsamad Saud A, Rudland Philip S, Malki Mohammed I, Ke Youqiang
The Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine.
Department of Biochemistry, Liverpool University, Liverpool L69 3GA, UK.
Precis Clin Med. 2019 Oct;2(3):192-196. doi: 10.1093/pcmedi/pbz015. Epub 2019 Sep 9.
In this short communication, a novel fatty acid-binding protein 5 (FABP5)-related signal transduction pathway in prostate cancer is reviewed. In castration-resistant prostate cancer (CRPC) cells, the FABP5-related signal transduction pathway plays an important role during transformation of the cancer cells from androgen-dependent state to androgen-independent state. The detailed route of this signal transduction pathway can be described as follows: when FABP5 expression is increased as the increasing malignancy, excessive amounts of fatty acids from intra- and extra-cellular sources are transported into the nucleus of the cancer cells where they act as signalling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ). The phosphorylated or biologically activated PPARγ then modulates the expression of its downstream target regulatory genes to trigger a series of molecular events that eventually lead to enhanced tumour expansion and aggressiveness caused by an overgrowth of the cancer cells with a reduced apoptosis and an increased angiogenesis. Suppressing the FABP5-related pathway via RNA interference against FABP5 has produced a 63-fold reduction in the average size of the tumours developed from CRPC cells in nude mice, a seven-fold reduction of tumour incidence, and a 100% reduction of metastasis rate. Experimental treatments of CRPC with novel FABP5 inhibitors have successfully inhibited the malignant progression of CRPC cells both and in nude mouse. These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.
在这篇简短的通讯中，对前列腺癌中一种新的脂肪酸结合蛋白5（FABP5）相关信号转导通路进行了综述。在去势抵抗性前列腺癌（CRPC）细胞中，FABP5相关信号转导通路在癌细胞从雄激素依赖状态转变为雄激素非依赖状态的过程中发挥重要作用。该信号转导通路的详细途径如下：随着恶性程度增加，FABP5表达升高，细胞内和细胞外来源的过量脂肪酸被转运到癌细胞核内，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）。磷酸化或具有生物学活性的PPARγ随后调节其下游靶调控基因的表达，引发一系列分子事件，最终导致肿瘤扩张增强和侵袭性增加，这是由于癌细胞过度生长、凋亡减少和血管生成增加所致。通过针对FABP5的RNA干扰抑制FABP5相关通路，使裸鼠体内由CRPC细胞形成的肿瘤平均大小降低了63倍，肿瘤发生率降低了7倍，转移率降低了100%。用新型FABP5抑制剂对CRPC进行实验性治疗，已成功抑制了CRPC细胞在体外和裸鼠体内的恶性进展。这些研究表明，FABP5相关信号转导通路是CRPC细胞治疗干预的一个新靶点。
