Ding Wei, Sun Jiaao, Song Shiyan, Cui Yuying, Chen Feng, Yuan Qihang, Shang Wei
First Affiliated Hospital of Dalian Medical University, Dalian, China.
Int J Surg. 2025 Jun 1;111(6):3920-3930. doi: 10.1097/JS9.0000000000002365. Epub 2025 Apr 1.
Junction plakoglobin (JUP) is a critical cell adhesion molecule implicated in mediating cell-cell adhesion. Cancer, characterized by the loss of normal cellular regulation, results in unchecked proliferation and the breakdown of cell-cell junctions, facilitating malignant cell invasion into surrounding tissues. Recent studies have highlighted the involvement of JUP in the transduction of various intercellular signaling pathways, underscoring its significant role in tumor initiation, progression, and prognosis. In contrast to its homolog β-catenin, the interplay between JUP and cancer remains underexplored. To clarify JUP's role and underlying mechanisms in cancer progression, this review examines recent advancements, focusing on JUP's regulation of key cancer-related signaling pathways, such as Wnt/β-catenin, p53, and cadherin-mediated pathways. The review also investigates JUP's relevance across various cancer types, including those of the reproductive, digestive, and urinary systems. Mechanistically, JUP exhibits context-dependent actions in different cancers, demonstrating dual roles in tumorigenesis. Lastly, the potential of JUP as a target for early diagnosis, effective treatment, and prognostic prediction in cancer is evaluated. In conclusion, targeting JUP offers a promising avenue for cancer therapy, providing valuable insights for future research.
桥粒斑珠蛋白(JUP)是一种关键的细胞粘附分子,参与介导细胞间粘附。癌症的特征是正常细胞调节功能丧失,导致细胞不受控制地增殖以及细胞间连接的破坏,从而促进恶性细胞侵入周围组织。最近的研究强调了JUP参与各种细胞间信号通路的转导,突显了其在肿瘤发生、发展和预后中的重要作用。与其同系物β-连环蛋白不同,JUP与癌症之间的相互作用仍未得到充分研究。为了阐明JUP在癌症进展中的作用及其潜在机制,本综述考察了最近的进展,重点关注JUP对关键癌症相关信号通路的调节,如Wnt/β-连环蛋白、p53和钙黏蛋白介导的通路。该综述还研究了JUP在各种癌症类型中的相关性,包括生殖系统、消化系统和泌尿系统的癌症。从机制上讲,JUP在不同癌症中表现出依赖于背景的作用,在肿瘤发生中显示出双重作用。最后,评估了JUP作为癌症早期诊断、有效治疗和预后预测靶点的潜力。总之,以JUP为靶点为癌症治疗提供了一条有前景的途径,为未来的研究提供了有价值的见解。