Huffman Nickelas, Palmieri Dario, Coppola Vincenzo
Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
J Oncol. 2019 Nov 30;2019:4216750. doi: 10.1155/2019/4216750. eCollection 2019.
Cancer cell plasticity is the ability of cancer cells to intermittently morph into different fittest phenotypic states. Due to the intrinsic capacity to change their composition and interactions, protein macromolecular complexes are the ideal instruments for transient transformation. This review focuses on a poorly studied mammalian macromolecular complex called the CTLH (carboxy-terminal to LisH) complex. Currently, this macrostructure includes 11 known members (ARMC8, GID4, GID8, MAEA, MKLN1, RMND5A, RMND5B, RANBP9, RANBP10, WDR26, and YPEL5) and it has been shown to have E3-ligase enzymatic activity. CTLH proteins have been linked to all fundamental biological processes including proliferation, survival, programmed cell death, cell adhesion, and migration. At molecular level, the complex seems to interact and intertwine with key signaling pathways such as the PI3-kinase, WNT, TGF, and NFB, which are key to cancer cell plasticity. As a whole, the CTLH complex is overexpressed in the most prevalent types of cancer and may hold the key to unlock many of the biological secrets that allow cancer cells to thrive in harsh conditions and resist antineoplastic therapy.
癌细胞可塑性是指癌细胞间歇性地转变为不同最适应表型状态的能力。由于蛋白质大分子复合物具有改变其组成和相互作用的内在能力，它们是实现瞬时转变的理想工具。本综述聚焦于一种研究较少的哺乳动物大分子复合物，即CTLH（LisH羧基末端）复合物。目前，这种宏观结构包含11个已知成员（ARMC8、GID4、GID8、MAEA、MKLN1、RMND5A、RMND5B、RANBP9、RANBP10、WDR26和YPEL5），并且已显示具有E3连接酶活性。CTLH蛋白与包括增殖、存活、程序性细胞死亡、细胞黏附和迁移在内的所有基本生物学过程相关。在分子水平上，该复合物似乎与关键信号通路如PI3激酶、WNT、TGF和NFκB相互作用并交织在一起，而这些信号通路是癌细胞可塑性的关键。总体而言，CTLH复合物在最常见的癌症类型中过度表达，可能是解开许多使癌细胞在恶劣条件下茁壮成长并抵抗抗肿瘤治疗的生物学秘密的关键。
