Pard3b-KO Mouse

PARD3B, a member of the Par-3/Baz family of polarity determinants, is highly conserved across metazoans. In vertebrates, it is specifically expressed in basal layer stem cells of stratified squamous epithelia where it localizes strictly at adherens junctions in many epithelia. It may contribute to clustering of E-cadherin, signalling from adherens junctions via Src family kinases, or mitotic spindle orientation by adherens junctions in response to mechanical forces [3].

In glioblastoma multiforme (GBM), expressions of AR and PARD3B mRNA and proteins in human GBM tissues are upregulated compared to normal human brain tissues, and there is a highly positive correlation between them. The testosterone AR-PARD3B signaling axis contributes to GBM tumorigenesis and malignance through stimulating cell proliferation and colony formation, as suppressing AR activity attenuates testosterone-induced PARD3B gene expression, cell proliferation, and colony formation in human glioblastoma cells [1]. In intrahepatic cholangiocarcinoma (ICC), VIRMA facilitates ICC progression by epigenetically augmenting TMED2 and PARD3B mRNA stabilization. VIRMA-induced expression of PARD3B activates the Akt/GSK/β-catenin and MEK/ERK/Slug signaling pathways, promoting ICC proliferation and metastasis [2].

In conclusion, PARD3B is involved in cell polarity and adhesion, and plays significant roles in diseases such as GBM and ICC. Studies related to PARD3B, including those potentially using gene knockout or other loss-of-function models, help reveal its functions in specific disease-related biological processes, providing potential therapeutic targets for these diseases.

References:

1. Yang, Jr-Di, Chen, Jui-Tai, Liu, Shing-Hwa, Chen, Ruei-Ming. 2022. Contribution of the Testosterone Androgen Receptor-PARD3B Signaling Axis to Tumorigenesis and Malignance of Glioblastoma Multiforme through Stimulating Cell Proliferation and Colony Formation. In Journal of clinical medicine, 11, . doi:10.3390/jcm11164818. https://pubmed.ncbi.nlm.nih.gov/36013056/

2. Xu, Hongfa, Lin, Xiaowen, Li, Zhongliang, Zhan, Meixiao, He, Ke. 2023. VIRMA facilitates intrahepatic cholangiocarcinoma progression through epigenetic augmentation of TMED2 and PARD3B mRNA stabilization. In Journal of gastroenterology, 58, 925-944. doi:10.1007/s00535-023-02015-5. https://pubmed.ncbi.nlm.nih.gov/37391589/

3. Thompson, Barry J. 2021. Par-3 family proteins in cell polarity & adhesion. In The FEBS journal, 289, 596-613. doi:10.1111/febs.15754. https://pubmed.ncbi.nlm.nih.gov/33565714/