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• W4323318879 abstract "Cancers, such as squamous cell carcinoma, frequently invade as multicellular units. However, these invading units can be organised in a variety of ways, ranging from thin discontinuous strands to thick ‘pushing’ collectives. Here we employ an integrated experimental and computational approach to identify the factors that determine the mode of collective cancer cell invasion. We find that matrix proteolysis is linked to the formation of wide strands but has little effect on the maximum extent of invasion. Cell-cell junctions also favour wide strands, but our analysis also reveals a requirement for cell-cell junctions for efficient invasion in response to uniform directional cues. Unexpectedly, the ability to generate wide invasive strands is coupled to the ability to grow effectively when surrounded by extracellular matrix in three-dimensional assays. Combinatorial perturbation of both matrix proteolysis and cell-cell adhesion demonstrates that the most aggressive cancer behaviour, both in terms of invasion and growth, is achieved at high levels of cell-cell adhesion and high levels of proteolysis. Contrary to expectation, cells with canonical mesenchymal traits – no cell-cell junctions and high proteolysis – exhibit reduced growth and lymph node metastasis. Thus, we conclude that the ability of squamous cell carcinoma cells to invade effectively is also linked to their ability to generate space for proliferation in confined contexts. These data provide an explanation for the apparent advantage of retaining cell-cell junctions in squamous cell carcinomas." @default.
• W4323318879 created "2023-03-07" @default.
• W4323318879 creator A5008596795 @default.
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• W4323318879 date "2023-03-09" @default.
• W4323318879 modified "2023-10-17" @default.
• W4323318879 title "Interplay of adherens junctions and matrix proteolysis determines the invasive pattern and growth of squamous cell carcinoma" @default.
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• W4323318879 doi "https://doi.org/10.7554/elife.76520" @default.
• W4323318879 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36892272" @default.
• W4323318879 hasPublicationYear "2023" @default.
• W4323318879 type Work @default.
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• W4323318879 hasAuthorship W4323318879A5015204242 @default.

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