PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 28, 2022
- Source ID
- 10.1083/jcb.202108083
Entities
People
- Arthur M Mercurio
- Choua Xiong
- Mengdie Wang
Organizations
- National Cancer Institute
- United States Department of Defense
- University of Massachusetts Medical School