Division of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai, China.
Mol Cancer Res. 2012 Apr;10(4):485-93. doi: 10.1158/1541-7786.MCR-11-0222. Epub 2012 Mar 27.
The structural proteins cytokeratin 18 (CK18) and its coexpressed complementary partner CK8 are expressed in a variety of adult epithelial organs and may play a role in carcinogenesis. In this study, we focused on the biological functions of CK18, which is thought to modulate intracellular signaling and operates in conjunction with various related proteins. CK18 may affect carcinogenesis through several signaling pathways, including the phosphoinositide 3-kinase (PI3K)/Akt, Wnt, and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathways. CK18 acts as an identical target of Akt in the PI3K/Akt pathway and of ERK1/2 in the ERK MAPK pathway, and regulation of CK18 by Wnt is involved in Akt activation. Finally, we discuss the importance of gaining a more complete understanding of the expression of CK18 during carcinogenesis, and suggest potential clinical applications of that understanding.
结构蛋白细胞角蛋白 18（CK18）及其共表达的互补伴侣 CK8 表达于多种成年上皮器官，可能在癌变过程中发挥作用。在这项研究中，我们专注于 CK18 的生物学功能，它被认为调节细胞内信号转导，并与各种相关蛋白协同作用。CK18 可能通过多种信号通路影响癌变，包括磷酸肌醇 3-激酶（PI3K）/Akt、Wnt 和细胞外信号调节激酶（ERK）丝裂原激活蛋白激酶（MAPK）信号通路。CK18 作为 PI3K/Akt 通路中 Akt 的相同靶标，以及 ERK MAPK 通路中 ERK1/2 的靶标，Wnt 对 CK18 的调节涉及 Akt 的激活。最后，我们讨论了更全面地了解 CK18 在癌变过程中的表达的重要性，并提出了对这种理解的潜在临床应用。
