法国巴黎文理研究大学Philippe Chavrier、Christophe Lamaze、Pedro Monteiro研究组合作在研究中取得进展。他们的最新研究表明机械敏感性穴样内陷-内吞体相互作用推动基质重塑并促进癌细胞侵袭。该项研究成果发表在2023年10月30日出版的《自然—细胞生物学》上。

研究人员描述了在二维和三维I型胶原基质环境以及癌细胞质膜与收缩纤维的接触部位，穴样内陷小体集群和基质降解性内吞体的独特并置。随着基质重塑，研究观察到穴样内陷小体与纤维直段之间以及内陷小体与纤维弯曲段之间优先结合。穴样内陷小体的招募先于内含体的形成和活动，并且是内含体形成和活动所必需的。反过来，内含体的破坏也会导致纤维相关穴样内陷的积累。

此外，穴样内陷小体和胶原受体β1整合素在纤维接触部位共定位，整合素控制穴样内陷小体向纤维的招募。反过来，穴样内陷小体又利用内陷依赖性和胶原蛋白清除依赖性机制介导β1整合素的清除和胶原蛋白的吸收。该数据揭示了穴样内陷小体和侵袭小体之间的相互作用，这种相互作用协调了对封闭纤维的粘附和蛋白水解重塑，从而有利于肿瘤细胞的扩散。

据了解，内吞体和穴样内陷小体是与癌细胞转移有关的机械敏感结构。

附：英文原文

Title: A mechanosensitive caveolae–invadosome interplay drives matrix remodelling for cancer cell invasion

Author: Monteiro, Pedro, Remy, David, Lemerle, Eline, Routet, Fiona, Mac, Anne-Sophie, Guedj, Chlo, Ladoux, Benoit, Vassilopoulos, Stphane, Lamaze, Christophe, Chavrier, Philippe

Issue&Volume: 2023-10-30

Abstract: Invadosomes and caveolae are mechanosensitive structures that are implicated in metastasis. Here, we describe a unique juxtaposition of caveola clusters and matrix degradative invadosomes at contact sites between the plasma membrane of cancer cells and constricting fibrils both in 2D and 3D type I collagen matrix environments. Preferential association between caveolae and straight segments of the fibrils, and between invadosomes and bent segments of the fibrils, was observed along with matrix remodelling. Caveola recruitment precedes and is required for invadosome formation and activity. Reciprocally, invadosome disruption results in the accumulation of fibril-associated caveolae. Moreover, caveolae and the collagen receptor β1 integrin co-localize at contact sites with the fibrils, and integrins control caveola recruitment to fibrils. In turn, caveolae mediate the clearance of β1 integrin and collagen uptake in an invadosome-dependent and collagen-cleavage-dependent mechanism. Our data reveal a reciprocal interplay between caveolae and invadosomes that coordinates adhesion to and proteolytic remodelling of confining fibrils to support tumour cell dissemination.

DOI: 10.1038/s41556-023-01272-z

Source: https://www.nature.com/articles/s41556-023-01272-z