Emergence of MUC1 in Mammals for Adaptation of Barrier Epithelia.
Emergence of MUC1 in Mammals for Adaptation of Barrier Epithelia.
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本文综述的证据表明，MUC 1-C在哺乳动物中进化，以促进屏障组织中延伸到常驻干细胞和免疫细胞的炎症适应。炎症记忆是一个重要的过程，保护屏障龛免受未来的侮辱。由自然选择引起的进化适应，例如MUC 1基因，可能有利于生存。然而，在慢性炎症环境中MUC 1-C的长期激活代表了促进癌症的不利适应。粘蛋白1（MUC 1）基因是基于其在人类乳腺癌中的过表达而发现的。随后的工作表明，MUC 1在来自其他不同器官的癌症中异常表达，包括皮肤和免疫细胞。这些发现支持MUC 1在屏障组织适应感染和环境应激中的作用。这种进化适应的根本重要性是包含SEA结构域，其催化MUC 1蛋白的自蛋白水解和非共价异二聚体复合物的形成。产生的MUC 1异源二聚体在顶端细胞膜处保持平衡，以响应稳态的丧失。复合物的破坏将MUC 1 N-末端（MUC 1-N）亚基释放到保护性粘液凝胶中。相反，跨膜C-末端（MUC 1-C）亚基激活谱系可塑性，表观遗传重编程和修复程序。这种MUC 1-C激活的程序显然是为屏障组织进化的，以建立与伤口愈合相关的自我调节增殖、炎症和重塑反应。新出现的证据表明，MUC 1-C支持组织干细胞和免疫细胞在屏障小生境中的炎症适应。本文综述了慢性炎症对MUC 1-C的长期激活如何通过建立驱动自我更新和致瘤性的自诱导节点来促进癌症干细胞（CSC）状态。
The evidence reviewed here indicates that MUC1-C evolved in mammals to promote inflammatory adaptation in barrier tissues that extends to resident stem cells and immune cells. Inflammatory memory is an essential process that protects barrier niches against future insults. Evolutionary adaptations arising from natural selection, as for example the MUC1 gene, can be beneficial for survival. However, prolonged activation of MUC1-C in settings of chronic inflammation represents an adverse adaptation that promotes cancer. The mucin 1 (MUC1) gene was discovered based on its overexpression in human breast cancers. Subsequent work demonstrated that MUC1 is aberrantly expressed in cancers originating from other diverse organs, including skin and immune cells. These findings supported a role for MUC1 in the adaptation of barrier tissues to infection and environmental stress. Of fundamental importance for this evolutionary adaptation was inclusion of a SEA domain, which catalyzes autoproteolysis of the MUC1 protein and formation of a non-covalent heterodimeric complex. The resulting MUC1 heterodimer is poised at the apical cell membrane to respond to loss of homeostasis. Disruption of the complex releases the MUC1 N-terminal (MUC1-N) subunit into a protective mucous gel. Conversely, the transmembrane C-terminal (MUC1-C) subunit activates a program of lineage plasticity, epigenetic reprogramming and repair. This MUC1-C-activated program apparently evolved for barrier tissues to mount self-regulating proliferative, inflammatory and remodeling responses associated with wound healing. Emerging evidence indicates that MUC1-C underpins inflammatory adaptation of tissue stem cells and immune cells in the barrier niche. This review focuses on how prolonged activation of MUC1-C by chronic inflammation in these niches promotes the cancer stem cell (CSC) state by establishing auto-inductive nodes that drive self-renewal and tumorigenicity.
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DOI：
10.1158/1541-7786.mcr-21-0672
发表时间：
2022-04-01
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Bhattacharya A;Fushimi A;Yamashita N;Hagiwara M;Morimoto Y;Rajabi H;Long MD;Abdulla M;Ahmad R;Street K;Liu S;Liu T;Kufe D
通讯作者：
Kufe D
影响因子：
4
作者：
Franke, FE;Kraus, S;Bergmann, M
通讯作者：
Bergmann, M
影响因子：
5.2
作者：
Raina D;Ahmad R;Rajabi H;Panchamoorthy G;Kharbanda S;Kufe D
通讯作者：
Kufe D
影响因子：
82.9
作者：
Furman, David;Campisi, Judith;Slavich, George M.
通讯作者：
Slavich, George M.
DOI：
10.1152/ajprenal.00127.2021
发表时间：
2021-08-01
影响因子：
4.2
作者：
Al-bataineh, Mohammad M.;Kinlough, Carol L.;Hughey, Rebecca P.
通讯作者：
Hughey, Rebecca P.