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.
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2 May 2022
Article|
March 28 2022
PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics
Mengdie Wang
,
Mengdie Wang
1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA
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Choua Xiong
,
Choua Xiong
1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA
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Arthur M. Mercurio
1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA
Correspondence to Arthur M. Mercurio: arthur.mercurio@umassmed.edu
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Mengdie Wang
1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA
Choua Xiong
1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA
Correspondence to Arthur M. Mercurio: arthur.mercurio@umassmed.edu
Received:
August 16 2021
Revision Received:
December 20 2021
Accepted:
February 16 2022
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
National Cancer Institute
- Award Id(s): CA168464,CA218085
Funder(s):
U.S. Department of Defense
- Award Id(s): W81XWH2110123
© 2022 Wang et al.
2022
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2022) 221 (5): e202108083.
Article history
Received:
August 16 2021
Revision Received:
December 20 2021
Accepted:
February 16 2022
Connected Content
Citation
Mengdie Wang, Choua Xiong, Arthur M. Mercurio; PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics. J Cell Biol 2 May 2022; 221 (5): e202108083. doi: https://doi.org/10.1083/jcb.202108083
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