Apical-basal polarity in tumor progression and metastasis

大多数人癌在从上皮细胞分化为上皮细胞的过程中， 良性到浸润性癌。顶-底极性常被认为是肿瘤的守门人 发展和转移。上皮-间充质转化（EMT）提供静止的癌细胞 在转移过程中侵袭和扩散的能力。虽然上皮细胞极性丧失是早期阶段， 在EMT过程中，极性在很大程度上被认为是EMT诱导信号的被动接受者， 减少上皮特征。很少有人知道顶基极性是否会直接影响 EMT转录因子作为反馈机制发挥作用，以控制肿瘤过程中的EMT进展 转移这项建议的重点是了解顶基极性调节的机制， 机械直接作为EMT的关键检查点来阻断肿瘤侵袭和转移。使用 小鼠和人上皮细胞三维类器官培养物具有完整的顶-基底极性，我们的目标是：1）阐明 顶基极性阻断EMT和侵袭的分子机制; 2）了解 PAR极性复合物调控EMT转录因子抑制EMT的发生; 3）研究PAR极性复合物是否参与EMT的发生。 顶基极性/EMT通路在乳腺癌侵袭转移中作用 进展

The majority of human carcinomas show loss of epithelial apical-basal polarity during the progression from benign to invasive carcinoma. Apical-basal polarity is often regarded as a gatekeeper against tumour development and metastasis. Epithelial-Mesenchymal Transition (EMT) provides stationary carcinoma cells the ability to invade and disseminate during metastasis. Although loss of epithelial cell polarity is an early step during the EMT process, polarity is largely thought to be a passive recipient of the EMT-inducing signals to decrease epithelial characteristics. Very little is known whether apical-basal polarity could directly impinge on the EMT transcription factors to function as feedback mechanisms to control EMT progression during tumor metastasis. This proposal focuses on understanding the mechanism by which apical-basal polarity regulatory machinery directly functions as a critical checkpoint of EMT to block tumor invasion and metastasis. Using mouse and human epithelial 3D organoid cultures with intact apical-basal polarity, we aim to 1) To elucidate the molecular mechanism by which apical-basal polarity blocks EMT and invasion; 2) To understand how the PAR polarity complex regulates EMT transcription factors to inhibit EMT; 3) To determine the involvement of the apical-basal polarity/EMT pathway in invasion and metastasis in vivo and in human breast cancer progression.