Palmitoylation: a protein S-acylation with implications for breast cancer.
Palmitoylation: a protein S-acylation with implications for breast cancer.
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DOI：
10.1038/npjbcancer.2016.28
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发表时间：
2016
影响因子：
5.9
通讯作者：
Ragan MA
中科院分区：
文献类型：
--
作者：
Anderson AM;Ragan MA
蛋白质s酰化是一种可逆的翻译后脂质修饰，主要通过硫酯键将脂肪酸链与半胱氨酸氨基酸连接。脂肪酸分子主要是棕榈酸酯，因此术语“棕榈酰化”更常用。棕榈酰化已被发现可以调节蛋白质功能的所有阶段，包括成熟加工、运输、膜锚定、信号传导范围和效力以及降解。在乳腺癌中，棕榈酰化已被证明可以控制常见的失调基因的功能，包括雌激素受体、表皮生长因子（EGF）受体家族和癌症干细胞标记物。重要的是，棕榈酰化是控制质膜复合物形成的关键因素，包括四跨蛋白、整合素和细胞间通讯的关键基因产物。在转移过程中，癌细胞通过与基质细胞和免疫细胞相互作用增强其转移能力。尽管异常棕榈酰化可能有助于肿瘤的发生和生长，但其在这些细胞-细胞相互作用中的潜在作用特别令人感兴趣，因为它可能提供转移的机制，包括癌细胞驱动的免疫调节。异常棕榈酰化在乳腺癌中的作用的令人信服的证据仍有待建立。为此，本文总结了新出现的证据，强调了相关的知识空白，并提出了未来研究的方向。
Protein S-acylation is a reversible post-translational lipid modification that involves linkage of a fatty acid chain predominantly to a cysteine amino acid via a thioester bond. The fatty acid molecule is primarily palmitate, thus the term ‘palmitoylation’ is more commonly used. Palmitoylation has been found to modulate all stages of protein function including maturational processing, trafficking, membrane anchoring, signaling range and efficacy, and degradation. In breast cancer, palmitoylation has been shown to control the function of commonly dysregulated genes including estrogen receptors, the epidermal growth factor (EGF) family of receptors, and cancer stem cell markers. Importantly, palmitoylation is a critical factor controlling the formation of complexes at the plasma membrane involving tetraspanins, integrins, and gene products that are key to cell–cell communication. During metastasis, cancer cells enhance their metastatic capacity by interacting with stroma and immune cells. Although aberrant palmitoylation could contribute to tumor initiation and growth, its potential role in these cell–cell interactions is of particular interest, as it may provide mechanistic insight into metastasis, including cancer cell-driven immune modulation. Compelling evidence for a role for aberrant palmitoylation in breast cancer remains to be established. To this end, in this review we summarize emerging evidence and highlight pertinent knowledge gaps, suggesting directions for future research.