School of Cancer and Pharmaceutical Sciences, Kings College London, London, UK.
Departments of Oncologic Pathology and Pathology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Small GTPases. 2021 Jul;12(4):265-272. doi: 10.1080/21541248.2020.1826781. Epub 2020 Oct 12.
Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for synthesis of the fatty acid palmitate; the building block for protein palmitoylation. A functional role for FASN in regulating cell proliferation is widely accepted. We recently reported that FASN activity can also mediate prostate cancer HGF-mediated cell motility. Moreover, we found that modulation of FASN expression specifically impacts on the palmitoylation of RhoU. Findings we will describe here. We now report that loss of FASN expression also impairs HGF-mediated cell dissociation responses. Taken together our results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.
脂肪酸合酶(FASN)在前列腺癌中普遍过表达,并与肿瘤进展相关。FASN 负责合成脂肪酸棕榈酸;蛋白质棕榈酰化的构建块。FASN 在调节细胞增殖中的功能作用已被广泛接受。我们最近报道,FASN 活性还可以介导前列腺癌 HGF 介导的细胞迁移。此外,我们发现 FASN 表达的调节会特异性影响 RhoU 的棕榈酰化。我们将在这里描述这些发现。我们现在报告说,FASN 表达的丧失也会损害 HGF 介导的细胞解离反应。总之,我们的研究结果提供了令人信服的证据,表明 FASN 活性直接促进细胞迁移,并支持 FASN 作为转移性前列腺癌的潜在治疗靶点。