Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Center for Comparative Respiratory Biology and Medicine, University of California Davis, Davis, CA, USA.
Cancer Metastasis Rev. 2017 Dec;36(4):737-747. doi: 10.1007/s10555-017-9709-6.
Emerging evidence implicates myristoylated alanine-rich C-kinase substrate (MARCKS), a major substrate of protein kinase C (PKC), in a critical role for cancer development and progression. MARCKS is tethered to the plasma membrane but can shuttle between the cytosol and plasma membrane via the myristoyl-electrostatic switch. Phosphorylation of MARCKS by PKC leads to its translocation from the plasma membrane to the cytosol where it functions in actin cytoskeletal remodeling, Ca signaling through binding to calmodulin, and regulation of exocytic vesicle release in secretory cells such as neurons and airway goblet cells. Although the contribution of MARCKS to various cellular processes has been extensively studied, its roles in neoplastic disease have been conflicting. This review highlights the molecular and functional differences of MARCKS that exist between normal and tumor cells. We also discuss the recent advances in the potential roles of MARCKS in tumorigenesis, metastasis, and resistance to anti-cancer therapies, with a focus on addressing the inconsistent results regarding the function of MARCKS as a promoter or inhibitor of oncogenesis.
新出现的证据表明，肉豆蔻酰化丙氨酸丰富的 C 激酶底物（MARCKS）是蛋白激酶 C（PKC）的主要底物，在癌症的发生和发展中起着关键作用。MARCKS 与质膜相连，但可以通过豆蔻酰-静电开关在细胞质和质膜之间穿梭。PKC 对 MARCKS 的磷酸化导致其从质膜转位到细胞质，在细胞质中，MARCKS 参与肌动蛋白细胞骨架重塑、通过与钙调蛋白结合的 Ca 信号转导，以及调节神经元和气道杯状细胞等分泌细胞的胞吐小泡释放。尽管 MARCKS 对各种细胞过程的贡献已得到广泛研究，但它在肿瘤疾病中的作用却存在矛盾。本综述强调了正常细胞和肿瘤细胞之间 MARCKS 的分子和功能差异。我们还讨论了 MARCKS 在肿瘤发生、转移和对抗癌治疗的耐药性中的潜在作用的最新进展，重点解决了关于 MARCKS 作为致癌促进因子或抑制剂的功能的不一致结果。
