1. Myristoylated alanine-rich C kinase substrate (MARCKS): a multirole signaling protein in cancers
- Author
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Fong, Lon Wolf R, Yang, David C, and Chen, Ching-Hsien
- Subjects
Cancer ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,Carcinogenesis ,Humans ,Myristoylated Alanine-Rich C Kinase Substrate ,Neoplasm Metastasis ,Neoplasms ,MARCKS ,Neoplastic growth ,Metastasis ,Drug resistance ,PI3K/AKT signaling ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
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, Ca2+ 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.
- Published
- 2017