Guan Liu-Yuan, Lv Jian-Qing, Zhang De-Qing, Li Bo
Applied Mechanics Laboratory, Department of Engineering Mechanics, Institute of Biomechanics and Medical Engineering, Tsinghua University, Beijing 100084, China.
Micromachines (Basel). 2021 Jan 22;12(2):112. doi: 10.3390/mi12020112.
Cell polarization, a process depending on both intracellular and intercellular interactions, is crucial for collective cell migration that commonly emerges in embryonic development, tissue morphogenesis, wound healing and cancer metastasis. Although invasive cancer cells display weak cell-cell interactions, they can invade host tissues through a collective mode. Yet, how cancer cells without stable cell-cell junctions polarize collectively to migrate and invade is not fully understood. Here, using a wound-healing assay, we elucidate the polarization of carcinoma cells at the population level. We show that with loose intercellular connections, the highly polarized leader cells can induce the polarization of following cancer cells and subsequent transmission of polarity information by membrane protrusions, leading to gradient polarization at the monolayer boundary. Unlike the polarization of epithelial monolayer where Rac1/Cdc42 pathway functions primarily, our data show that collective polarization of carcinoma cells is predominantly controlled by Golgi apparatus, a disruption of which results in the destruction of collective polarization over a large scale. We reveal that the Golgi apparatus can sustain membrane protrusion formation, polarized secretion, intracellular trafficking, and F-actin polarization, which contribute to collective cancer cell polarization and its transmission between cells. These findings could advance our understanding of collective cancer invasion in tumors.
细胞极化是一个依赖于细胞内和细胞间相互作用的过程，对于集体细胞迁移至关重要，集体细胞迁移常见于胚胎发育、组织形态发生、伤口愈合和癌症转移过程中。尽管侵袭性癌细胞表现出较弱的细胞间相互作用，但它们可以通过集体模式侵入宿主组织。然而，没有稳定细胞间连接的癌细胞如何集体极化以迁移和侵袭，目前尚未完全了解。在这里，我们使用伤口愈合试验，在群体水平上阐明癌细胞的极化情况。我们发现，在细胞间连接松散的情况下,高度极化的前导细胞可以诱导后续癌细胞的极化，并通过膜突起传递极性信息，从而在单层边界处形成梯度极化。与上皮单层细胞的极化不同（上皮单层细胞极化主要由Rac1/Cdc42信号通路发挥作用），我们的数据表明，癌细胞的集体极化主要由高尔基体控制，高尔基体的破坏会导致大规模的集体极化破坏。我们发现，高尔基体可以维持膜突起的形成、极化分泌、细胞内运输和F-肌动蛋白极化，这些因素有助于癌细胞的集体极化及其在细胞间的传递。这些发现可能会加深我们对肿瘤中癌细胞集体侵袭的理解。
