Du Fangqian, Xie Yuwei, Wu Shengze, Ji Mengling, Dong Bingzi, Zhu Chengzhan
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Department of Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
J Hepatocell Carcinoma. 2024 Sep 25;11:1801-1821. doi: 10.2147/JHC.S483861. eCollection 2024.
Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed.
肝胆胰疾病在全球范围内正变得越来越普遍，且相关癌症易于复发和转移。为了进行更准确的治疗，迫切需要新的治疗策略。紧密连接蛋白（CLDN）家族是一类膜蛋白，是紧密连接的主要成分，对于形成细胞间屏障和维持细胞极性至关重要。在哺乳动物中，紧密连接蛋白家族包含至少27种跨膜蛋白，在介导细胞黏附和细胞旁通透性方面起主要作用。多种紧密连接蛋白在各种癌症中发生改变，包括胃癌（GC）、食管癌（EC）、肝细胞癌（HCC）、胰腺癌（PC）、结直肠癌（CRC）和乳腺癌（BC）。越来越多的研究表明，紧密连接蛋白与肝胆胰疾病的发生和发展密切相关。有趣的是，紧密连接蛋白在不同肿瘤组织中对癌症进展表现出不同的作用，包括肿瘤抑制和促进作用。此外，目前正在研究各种紧密连接蛋白作为潜在的诊断和治疗靶点，包括紧密连接蛋白-3、紧密连接蛋白-4、紧密连接蛋白-18.2等。本文综述了紧密连接蛋白家族在肝胆胰疾病中的功能表型、分子机制和靶向应用，重点关注紧密连接蛋白-1、紧密连接蛋白-4、紧密连接蛋白-7和紧密连接蛋白-18.2，并提出了现状和未来前景。
