Department of Clinical Bio-resource Research and Development, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Cancer Sci. 2022 Nov;113(11):3657-3663. doi: 10.1111/cas.15549. Epub 2022 Sep 14.
Apico-basal polarity is a fundamental property of the epithelium that functions as a barrier, holds cells together, and determines the directions of absorption and secretion. Apico-basal polarity is regulated by extracellular matrix-integrin binding and downstream signaling pathways, including focal adhesion kinase, rouse-sarcoma oncogene (SRC), and RHO/RHO-associated kinase (ROCK). Loss of epithelial cell polarity plays a critical role in the progression of cancer cells. However, in differentiated carcinomas, polarity is not completely lost but dysregulated. Recent progress with a three-dimensional culture of primary cancer cells allowed for studies of the mechanism underlying the abnormality of polarity in differentiated cancers, including flexible switching of polarity status in response to the microenvironment. Invasive micropapillary carcinoma (MPC) is one of the histopathological phenotypes of adenocarcinoma, which is characterized by inverted polarity. Aberrant activation of RHO-ROCK signaling plays a critical role in the MPC phenotype. Establishing in vitro models will contribute to future drug targeting of the abnormal polarity status in cancer.
顶端-基底极性是上皮细胞的基本属性，它作为屏障，将细胞保持在一起，并决定吸收和分泌的方向。顶端-基底极性受细胞外基质-整合素结合和下游信号通路的调节，包括粘着斑激酶、 Rous 肉瘤癌基因 (Src) 和 RHO/ RHO 相关激酶 (ROCK)。上皮细胞极性的丧失在癌细胞的进展中起着关键作用。然而，在分化的癌中，极性并没有完全丧失，而是失调了。利用原代癌细胞的三维培养的最新进展，使得研究分化癌中极性异常的机制成为可能，包括对微环境的极性状态的灵活切换。浸润性微乳头状癌 (MPC) 是腺癌的组织病理学表型之一，其特征是极性倒置。RHO-ROCK 信号的异常激活在 MPC 表型中起着关键作用。建立体外模型将有助于未来针对癌症中异常极性状态的药物靶向治疗。
