角化包膜前体蛋白与癌症发生发展的研究进展

Research Progress of Keratocapsular Precursor Protein in the Development of Cancer

摘要: 角化包膜(cornified envelope, CE)前体蛋白是角化包膜的关键成分，对上皮屏障功能具有重要作用，可保护底层组织免受多种不利因素的影响。CE前体蛋白(包括兜甲蛋白、富含脯氨酸的小蛋白、内披蛋白、包膜蛋白、外周蛋白)经转谷氨酰胺酶交联形成刚性蛋白网络，并与ω-羟基神经酰胺共价键合，共同维系表皮屏障的完整性。近年来，越来越多的研究表明CE前体蛋白表达失调在癌症发生中扮演关键角色，不仅可能破坏物理屏障功能，还可能通过加剧氧化应激、增加基因组不稳定性以及增强致癌物渗透性等途径促进癌症发展。本文系统地综述了CE前体蛋白在癌前病变及恶性肿瘤中的作用机制及其临床意义，以期为靶向CE前体蛋白的癌症防治策略提供理论支持。

Abstract: As the key components of the cornified envelope (CE), cornified envelope precursor proteins play an important role in the epithelial barrier function and protect underlying tissues from a range of adverse factors. CE precursor proteins (including loricrin, small proline-rich proteins, involucrin, envoplakin and periplakin) are cross-linked by transglutaminases to form a rigid protein network and are covalently bonded to ω-hydroxy ceramides, collectively maintaining the integrity of the epidermal barrier. In recent years, accumulating evidence has shown that dysregulated CE precursor protein expression plays a key role in carcinogenesis and may not only potentially compromise the physical barrier function; it may also promote cancer development by exacerbating oxidative stress, increasing genomic instability, and enhancing carcinogen permeability. This review systematically summarizes the mechanistic and clinical significance of CE precursor proteins in precancerous lesions and malignant tumors, aiming to provide theoretical support for cancer prevention and treatment strategies targeting CE precursor proteins.