Atashrazm Farzaneh, Ellis Sarah
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, VIC, Australia.
Oncogene. 2021 Jun;40(25):4245-4262. doi: 10.1038/s41388-021-01813-6. Epub 2021 Jun 7.
Tissue disorganisation is one of the main hallmarks of cancer. Polarity proteins are responsible for the arrangement of cells within epithelial tissues through the asymmetric organisation of cellular components. Partition defective 3 (PARD3) is a master regulator of the Par polarity complex primarily due to its ability to form large complexes via its self-homologous binding domain. In addition to its role in polarity, PARD3 is a scaffolding protein that binds to intracellular signalling molecules, many of which are frequently deregulated in cancer. The role of PARD3 has been implicated in multiple solid cancers as either a tumour suppressor or promoter. This dual functionality is both physiologically and cell context dependent. In this review, we will discuss PARD3's role in tumourigenesis in both laboratory and clinical settings. We will also review several of the mechanisms underpinning PARD3's function including its association with intracellular signalling pathways and its role in the regulation of asymmetric cell division.
组织紊乱是癌症的主要特征之一。极性蛋白通过细胞成分的不对称组织负责上皮组织内细胞的排列。分隔缺陷3（PARD3）是Par极性复合体的主要调节因子，主要是因为它能够通过其自身同源结合域形成大型复合体。除了在极性方面的作用外，PARD3还是一种支架蛋白，可与细胞内信号分子结合，其中许多信号分子在癌症中经常失调。PARD3的作用在多种实体癌中被认为是肿瘤抑制因子或促进因子。这种双重功能取决于生理和细胞环境。在本综述中，我们将讨论PARD3在实验室和临床环境中肿瘤发生中的作用。我们还将综述支撑PARD3功能的几种机制，包括其与细胞内信号通路的关联及其在不对称细胞分裂调节中的作用。
