Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA.
J Cell Biol. 2022 May 2;221(5). doi: 10.1083/jcb.202108083. Epub 2022 Mar 28.
Although the immune checkpoint function of PD-L1 has dominated its study, we report that PD-L1 has an unanticipated intrinsic function in promoting the dynamics of persistent cell migration. PD-L1 concentrates at the rear of migrating carcinoma cells where it facilitates retraction, resulting in the formation of PD-L1-containing retraction fibers and migrasomes. PD-L1 promotes retraction by interacting with and localizing the β4 integrin to the rear enabling this integrin to stimulate contractility. This mechanism involves the ability of PD-L1 to maintain cell polarity and lower membrane tension at the cell rear compared with the leading edge that promotes the localized interaction of PD-L1 and the β4 integrin. This interaction enables the β4 integrin to engage the actin cytoskeleton and promote RhoA-mediated contractility. The implications of these findings with respect to cell-autonomous functions of PD-L1 and cancer biology are significant.
虽然 PD-L1 的免疫检查点功能占据了其研究的主导地位，但我们报告称，PD-L1 在促进持久细胞迁移的动力学方面具有意想不到的内在功能。PD-L1 集中在迁移癌细胞的后部，在那里它促进收缩，导致形成含有 PD-L1 的回缩纤维和迁移体。PD-L1 通过与β4 整合素相互作用并将其定位在后部来促进收缩，从而使该整合素能够刺激收缩性。这种机制涉及 PD-L1 维持细胞极性和降低细胞后部膜张力的能力，与促进 PD-L1 和β4 整合素局部相互作用的前缘相比。这种相互作用使β4 整合素能够与肌动蛋白细胞骨架结合，并促进 RhoA 介导的收缩性。这些发现对 PD-L1 的细胞自主功能和癌症生物学具有重要意义。
