Collective cell migration (CCM), in which cell-cell integrity remains preserved during movement, plays an important role in the progression of cancer. However, studies describing CCM in cancer progression are majorly focused on the effects of extracellular tissue components on moving cell plasticity. The molecular and cellular mechanisms of CCM during cancer progression remain poorly explored. Here, we report that proteolipid protein 2 (PLP2), a colonic epithelium-enriched transmembrane protein, plays a vital role in the CCM of invasive human colorectal cancer (CRC) epithelium by modulating leading-edge cell dynamics in 2D. The extracellular pool of PLP2, secreted via exosomes, was also found to contribute to the event. During CCM, the protein was found to exist in association with ZO-1 (also known as TJP1) and to be involved in the positioning of the latter at the migrating edge. PLP2-mediated positioning of ZO-1 at the leading edge further alters actin cytoskeletal organization that involves Rac1 activation. Taken together, our findings demonstrate that PLP2, via its association with ZO-1, drives CCM in CRC epithelium by modulating the leading-edge actin cytoskeleton, thereby opening up new avenues of cancer research. This article has an associated First Person interview with the first author of the paper.

中文翻译：

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PLP2 在人类结直肠癌细胞的前沿通过 ZO-1 介导的细胞骨架重塑驱动集体细胞迁移。

集体细胞迁移 (CCM)，其中细胞-细胞完整性在运动过程中保持不变，在癌症的进展中起着重要作用。然而，描述 CCM 在癌症进展中的研究主要集中在细胞外组织成分对移动细胞可塑性的影响。癌症进展过程中 CCM 的分子和细胞机制仍未得到很好的探索。在这里，我们报告蛋白脂质蛋白 2 (PLP2) 是一种富含结肠上皮的跨膜蛋白，它通过调节二维中的前沿细胞动力学在侵袭性人类结肠直肠癌 (CRC) 上皮的 CCM 中发挥重要作用。还发现通过外泌体分泌的 PLP2 的细胞外池也促成了这一事件。在 CCM 期间，发现该蛋白质与 ZO-1（也称为 TJP1）相关，并参与将后者定位在迁移边缘。PLP2 介导的 ZO-1 在前沿的定位进一步改变了涉及 Rac1 激活的肌动蛋白细胞骨架组织。总之，我们的研究结果表明，PLP2 通过与 ZO-1 的结合，通过调节前沿肌动蛋白细胞骨架来驱动 CRC 上皮细胞中的 CCM，从而开辟了癌症研究的新途径。本文与论文的第一作者进行了相关的第一人称采访。通过调节前沿肌动蛋白细胞骨架来驱动 CRC 上皮细胞中的 CCM，从而开辟癌症研究的新途径。本文与论文的第一作者进行了相关的第一人称采访。通过调节前沿肌动蛋白细胞骨架来驱动 CRC 上皮细胞中的 CCM，从而开辟癌症研究的新途径。本文与论文的第一作者进行了相关的第一人称采访。