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MINI REVIEW article

Front. Cell Dev. Biol.

Sec. Cell Adhesion and Migration

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1644011

Invadosomes as 'shape-shi0ers' of cellular matura7on: insights from megakaryocytes

Provisionally accepted
  • 1CBI, CNRS, Center of integrated biologie, UMR 5077 Molecular and cellular development, Toulouse, France, Toulouse, France
  • 2Centre de Biologie Integrative, Toulouse, France

The final, formatted version of the article will be published soon.

Invadosomes are a family of subcellular actin-based structures essential for cell-extracellular matrix (ECM) interaction and remodeling. In non-invasive cells, they are referred to as podosomes, which enable adhesion, migration, and ECM remodeling via secretion of metalloproteinases or mechano-traction. In invasive tumoral cells, these structures are called invadopodia due to their function. While structurally similar, podosomes appear as highly regular dots in 2D, and do not always exhibit ECM-degradative abilities, hence the term 'degradative dot-podosomes' used in this paper. Invadopodia are consistently degradative, fewer in number, slightly larger, deeper, less regular shape and longer-lived. In tumor cells, collagen I induces the formation of linear invadosomes, which promote invasion by degrading collagen through the action of MT1-MMP metalloproteinase and the adaptor protein Tks5.Interestingly, linear invadosomes also appear in non-tumor cells, such as megakaryocytes (MKs), the platelets precursors, that display podosomes, that closely resemble invadopodia. As MKs mature, Tks5 expression decreases, and dot-podosomes align along collagen I fibers, fusing into linear podosomes that remodel the ECM through mechanical traction and have lost degradative ability. The GTPase Cdc42, crucial for invadosomes formation, remains highly active in MKs internal demarcation membrane system (DMS), but is downregulated in linear podosomes.These observations suggest that Tks5, viewed as a marker of metastatic potential, also plays roles in normal physiology. Thus, linear podosomes with mechanotransductive properties may exist in a broader range of non-transformed cells. This mini-review focuses on the linear subfamily of invadosomes, highlighting their structure and function in MKs, a model in which invadosomes remain underexplored.

Keywords: linear invadosomes, podosomes, Cytoskeleton, Extracellular Matrix, metalloproteinase, CDC42 GTPase, collagene I, Megakaryocytes

Received: 09 Jun 2025; Accepted: 16 Jul 2025.

Copyright: © 2025 Gaits-Iacovoni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Frederique Gaits-Iacovoni, CBI, CNRS, Center of integrated biologie, UMR 5077 Molecular and cellular development, Toulouse, France, Toulouse, 31432 cedex 4, France

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