Fondazione Italiana Fegato - ONLUS, Liver Research Center, 34149 Trieste, Italy.
Front Biosci (Landmark Ed). 2022 May 20;27(5):164. doi: 10.31083/j.fbl2705164.
Discs large MAGUK scaffold protein 5 (DLG5) is a multi-domain member of membrane-associated guanylate kinase (MAGUK) family, which plays a major role in the maintenance of cell epithelial polarity being part of the SCRIB-LGL-DLG complex. Although polarity proteins have been generally considered tumor suppressors, recent discoveries led to reconsidering their role in cancer. This is also true for DLG5 in different cancer types, including hepatocellular carcinoma (HCC). In this cancer, DLG5 was negatively associated with malignant characteristics, however recent findings associated DLG5 expression with advanced stages of HCC. studies evidenced its possible role in sustaining cell growth and migration by the interaction with several intracellular pathways, such as Hippo, Hedgehog, and PI3K/AKT signaling pathways. In this review, we summarize the recent finding on the dual role of DLG5 and other polarity proteins in cancers. What emerges is a still undefined role of those proteins in cancers, especially in HCC, one of the most frequent cancers worldwide, where the function of DLG5 and other polarity proteins is still largely unexplored.
大 MAGUK 支架蛋白 5（DLG5）是膜相关鸟苷酸激酶（MAGUK）家族的多结构域成员，作为 SCRIB-LGL-DLG 复合物的一部分，在维持细胞上皮极性方面发挥着重要作用。尽管极性蛋白通常被认为是肿瘤抑制因子，但最近的发现促使人们重新考虑它们在癌症中的作用。这同样适用于不同癌症类型中的 DLG5，包括肝细胞癌（HCC）。在这种癌症中，DLG5 与恶性特征呈负相关，但最近的研究发现 DLG5 的表达与 HCC 的晚期阶段相关。研究表明，它通过与 Hippo、Hedgehog 和 PI3K/AKT 信号通路等几种细胞内途径相互作用，可能在维持细胞生长和迁移中发挥作用。在这篇综述中，我们总结了 DLG5 和其他极性蛋白在癌症中的双重作用的最新发现。出现的情况是，这些蛋白在癌症中的作用仍然不明确，尤其是在 HCC 中，HCC 是全球最常见的癌症之一，DLG5 和其他极性蛋白的功能在很大程度上仍未得到探索。
