PALMITOYLATION SIGNATURE IN PROSTATE CANCER CELL LINES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 脂肪酸代谢的改变是癌症，尤其是前列腺癌的常见特征。 在肿瘤细胞中，大多数脂肪酸由脂肪酸合成酶（FATCH）从头合成， 而在正常组织中，大部分脂肪酸是通过饮食和脂肪酸提供的。 表情几乎无法察觉。在前列腺肿瘤中，尽管周围环境中 在脂肪酸中，脂肪酸被大量表达。我们的研究小组和其他研究表明， 过表达FXR的肿瘤表现出侵袭性生物学行为。通过抑制凝血因子 siRNA或化学抑制剂导致肿瘤细胞凋亡。抑制剂的作用是损害 第七个催化位点，停止其最丰富的产物的生产， 棕榈酸盐重要的是，抑制剂的细胞生长抑制和凋亡作用被挽救 当棕榈酸盐加入细胞时。 脂肪酰化，即通过添加脂肪酸的蛋白质修饰，是蛋白质的一个共同特征。 真核细胞具体来说，棕榈酰化是长链的翻译后添加， 脂肪酸通过硫酯键连接到半胱氨酸残基。棕榈酰化是一个可逆的过程， 它允许蛋白质的快速调节，类似于磷酸化。关键信令 已知参与癌症的蛋白质是棕榈酰化的，例如Ras、Src家族 成员（即p59 fyn或p56 lck）和Wnt。棕榈酸的加入是一个信号， 膜定位，也用于调节突触、跨膜蛋白 和信号肽。 由于FGFAP抑制的作用如细胞凋亡或体内生长停滞，可以部分地被抑制。 我们提出癌细胞可能依赖于棕榈酸代谢， 保持其恶性表型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Altered fatty acid metabolism is a common feature of cancers, especially prostate cancer. In tumor cells, most fatty acids are synthesized de novo by fatty acid synthase (FASN), whereas in normal tissue, most of the fatty acids are supplied through the diet and FASN expression is almost undetectable. In prostate tumors, despite the high levels of ambient fatty acids, FASN is abundantly expressed. Our group and others showed that prostate tumors overexpressing-FASN display aggressive biological behavior. Inhibition of FASN via siRNA or chemical inhibitors, results in tumor apoptosis. The inhibitors act impairing one of the seven catalytic site of FASN, halting the production of its most abundant product, palmitate. Importantly, the cytostatic and apoptotic effects of the inhibitors are rescued when palmitate is added to the cells. Fatty acylation, i.e. protein modification by addition of fatty acids, is a common feature of eukaryotic cells. Specifically, palmitoylation is the posttranslational addition of long chain fatty acid to a cysteine residue via thioester linkage. Palmitoylation is a reversible process, and it allows for rapid regulation of protein, similar to phosphorylation. Critical signaling proteins involved in cancer are known to be palmitoylated such as Ras, Src family members (i.e. p59fyn or p56lck) and Wnt. Addition of palmitate is a signal for cellular membrane localization and is also exploited to regulate synapses, transmembrane proteins and signaling peptides. Since the effects of FASN inhibition like apoptosis or in vivo growth arrest, can be partially rescued by palmitate we proposed that cancer cells might rely on palmitate metabolism to maintain their malignant phenotype.