Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: uptake of radiolabeled acetate as a predictor of the targeted therapy outcome.
Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: uptake of radiolabeled acetate as a predictor of the targeted therapy outcome.
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DOI：
10.1371/journal.pone.0064570
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Saga T
中科院分区：
文献类型：
--
作者：
Yoshii Y;Furukawa T;Oyama N;Hasegawa Y;Kiyono Y;Nishii R;Waki A;Tsuji AB;Sogawa C;Wakizaka H;Fukumura T;Yoshii H;Fujibayashi Y;Lewis JS;Saga T
脂肪酸合成酶（FATIGATION）的表达在几种癌症中升高，这种过度表达与不良预后相关。据报道，Festival的抑制剂，如奥利司他，对过表达Festival的癌症显示出抗肿瘤作用，使Festival成为有希望的治疗靶点。然而，已经观察到个体肿瘤中FASN表达水平的巨大变化，并且需要在治疗前预测FASN靶向治疗结果的方法以避免不必要的治疗。此外，抑制FGFAP如何影响肿瘤进展仍不清楚。在这里，我们展示了使用放射性标记的乙酸盐摄取来预测FASN靶向治疗结果的方法，并提出了人前列腺癌细胞系的FASN抑制机制，以提供FASN靶向治疗的治疗策略。我们发现，放射性标记的醋酸盐的肿瘤摄取反映了FASN表达水平和对奥利司他体外和体内FASN靶向治疗的敏感性。FASN靶向治疗对具有高表达的肿瘤显著有效，这由高乙酸盐摄取指示。为了研究其机制，我们通过转导针对FERN 1的短发夹RNA建立了FERN 1敲除前列腺癌细胞，并通过形态学和细胞行为分析以及基于微阵列的基因表达谱分析来研究其特征。抑制FGFAP不仅抑制细胞增殖，而且阻止伪足形成，抑制细胞粘附、迁移和侵袭。FcB抑制还抑制了参与细胞内第二信使花生四烯酸和雄激素产生的基因，这两者都促进肿瘤进展。总的来说，我们的数据表明，放射性标记的醋酸盐的摄取是一个有用的预测FASN靶向治疗的结果。这表明，[1- 11 C]醋酸盐正电子发射断层扫描（PET）可能是一种强大的工具，通过非侵入性可视化肿瘤醋酸盐摄取和选择反应性肿瘤来实现个性化的FASN靶向治疗。FASN靶向治疗可能是一种有效的治疗方法，可以抑制与[1- 11 C]乙酸PET选择的前列腺癌肿瘤进展相关的多个步骤。
Fatty acid synthase (FASN) expression is elevated in several cancers, and this over-expression is associated with poor prognosis. Inhibitors of FASN, such as orlistat, reportedly show antitumor effects against cancers that over-express FASN, making FASN a promising therapeutic target. However, large variations in FASN expression levels in individual tumors have been observed, and methods to predict FASN-targeted therapy outcome before treatment are required to avoid unnecessary treatment. In addition, how FASN inhibition affects tumor progression remains unclear. Here, we showed the method to predict FASN-targeted therapy outcome using radiolabeled acetate uptake and presented mechanisms of FASN inhibition with human prostate cancer cell lines, to provide the treatment strategy of FASN-targeted therapy. We revealed that tumor uptake of radiolabeled acetate reflected the FASN expression levels and sensitivity to FASN-targeted therapy with orlistat in vitro and in vivo. FASN-targeted therapy was noticeably effective against tumors with high FASN expression, which was indicated by high acetate uptake. To examine mechanisms, we established FASN knockdown prostate cancer cells by transduction of short-hairpin RNA against FASN and investigated the characteristics by analyses on morphology and cell behavior and microarray-based gene expression profiling. FASN inhibition not only suppressed cell proliferation but prevented pseudopodia formation and suppressed cell adhesion, migration, and invasion. FASN inhibition also suppressed genes involved in production of intracellular second messenger arachidonic acid and androgen hormones, both of which promote tumor progression. Collectively, our data demonstrated that uptake of radiolabeled acetate is a useful predictor of FASN-targeted therapy outcome. This suggests that [1-11C]acetate positron emission tomography (PET) could be a powerful tool to accomplish personalized FASN-targeted therapy by non-invasive visualization of tumor acetate uptake and selection of responsive tumors. FASN-targeted therapy could be an effective treatment to suppress multiple steps related to tumor progression in prostate cancers selected by [1-11C]acetate PET.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
11.2
作者：
Nagasaki, Shuji;Suzuki, Takashi;Sasano, Hironobu
通讯作者：
Sasano, Hironobu
DOI：
10.4111/kju.2011.52.7.461
发表时间：
2011-07-01
期刊：
KOREAN JOURNAL OF UROLOGY
影响因子：
--
作者：
Choi, Joon Il;Kim, Yun Beom;Jung, Tae Young
通讯作者：
Jung, Tae Young
DOI：
10.1007/s00259-008-0981-0
发表时间：
2009-03-01
影响因子：
9.1
作者：
Oyama, Nobuyuki;Okazawa, Hidehiko;Yokoyama, Osamu
通讯作者：
Yokoyama, Osamu
影响因子：
6.4
作者：
Carvalho, Marco A.;Zecchin, Karina G.;Graner, Edgard
通讯作者：
Graner, Edgard