3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration
3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration
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DOI：
10.1016/j.celrep.2023.113554
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发表时间：
2023-12-14
期刊：
影响因子：
8.8
通讯作者：
Zech，Tobias
中科院分区：
文献类型：
--
作者：
Newman，Daniel;Young，Lorna E.;Zech，Tobias
细胞侵袭是一个多步骤的过程，由获得迁移表型和在复杂的3D细胞外环境中移动的能力启动。我们确定了三维矩阵中浸润性乳腺癌细胞的细胞-基质粘附复合物的组成，并确定了浸润性迁移所需的相互作用复合物。βPix和肌球蛋白18 A（Myo 18 A）驱动非肌肉肌球蛋白2A（NM 2A）极化募集至突起尖端的粘附复合物。肌动球蛋白力接合然后从桩蛋白中置换Git 1-βPix复合物，建立粘附成熟的反馈回路。我们观察到主动力传递到细胞核在侵入性迁移，这是需要向前拉细胞核。NM 2A向粘连的募集产生了非肌肉肌球蛋白同种型梯度，其从突起延伸到核。我们假设，这种梯度有利于耦合的细胞-基质相互作用的细胞前与核运动，使有效的侵入性迁移和前后细胞极性。
Cell invasion is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through complex 3D extracellular environments. We determine the composition of cell-matrix adhesion complexes of invasive breast cancer cells in 3D matrices and identify an interaction complex required for invasive migration. βPix and myosin18A (Myo18A) drive polarized recruitment of non-muscle myosin 2A (NM2A) to adhesion complexes at the tips of protrusions. Actomyosin force engagement then displaces the Git1-βPix complex from paxillin, establishing a feedback loop for adhesion maturation. We observe active force transmission to the nucleus during invasive migration that is needed to pull the nucleus forward. The recruitment of NM2A to adhesions creates a non-muscle myosin isoform gradient, which extends from the protrusion to the nucleus. We postulate that this gradient facilitates coupling of cell-matrix interactions at the protrusive cell front with nuclear movement, enabling effective invasive migration and front-rear cell polarity.