Proteolytic and mechanical remodeling of the extracellular matrix by invadopodia in cancer.
Proteolytic and mechanical remodeling of the extracellular matrix by invadopodia in cancer.
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DOI：
10.1088/1478-3975/aca0d8
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发表时间：
2022-11-21
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影响因子：
2
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中科院分区：
文献类型：
--
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肿瘤的侵袭和转移需要邻近细胞外基质（ECM）的重塑。在这篇简短的综述中，我们将介绍癌细胞对ECM的蛋白水解降解和机械重塑的机制，重点是侵过性。侵足是癌细胞特有的膜突起，其特征是肌动蛋白核心和通过MMPs局部降解ECM。虽然ECM也可以通过局灶粘连或内部胶原消化在较低水平上进行重塑，但目前认为浸润性是癌细胞降解mmp依赖性细胞外ECM的主要机制。最近的证据表明，上皮-间质转化（epithelial-mesenchymal transition， EMT）的完成对于侵袭和转移可能是必不可少的，并且侵袭不仅是间质、单细胞侵袭所必需的，也是集体侵袭所必需的。在集体入侵过程中，invadopodia被证明位于领导细胞中，允许跟随细胞通过合作移动。总的来说，这表明侵过性功能可能不仅是转移后期的必要条件，也是上皮细胞早期侵入间质组织的必要条件。在过去的十年中，侵过体研究已经过渡到3D和体内环境，从而在临床前动物模型中证实了它们在转移中的重要作用。综上所述，侵过性足可能作为转移的预后标记物和治疗靶点，具有很大的个体风险评估潜力。
Cancer invasion and metastasis require remodeling of the adjacent extracellular matrix (ECM). In this mini review, we will cover the mechanisms of proteolytic degradation and the mechanical remodeling of the ECM by cancer cells, with a focus on invadopodia. Invadopodia are membrane protrusions unique to cancer cells, characterized by an actin core and by the focal degradation of ECM via MMPs. While ECM can also be remodeled, at lower levels, by focal adhesions, or internal collagen digestion, invadopodia are now recognized as the major mechanism for MMP-dependent pericellular ECM degradation by cancer cells. Recent evidence suggests that the completion of epithelial-mesenchymal transition (EMT) may be dispensable for invadopodia and metastasis, and that invadopodia are required not only for mesenchymal, single cell invasion, but also for collective invasion. During collective invasion, invadopodia was then shown to be located in leader cells, allowing follower cells to move via cooperation. Collectively, this suggests that invadopodia function may be a requirement not only for later steps of metastasis, but also for early invasion of epithelial cells into the stromal tissue. Over the last decade, invadopodia studies have transitioned into in 3D and in vivo settings, leading to the confirmation of their essential role in metastasis in preclinical animal models. In summary, invadopodia may hold a great potential for individual risk assessment as a prognostic marker for metastasis, as well as a therapeutic target.
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