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Here, we show that such interface\u2010instructed phenotype switching represents a common feature across triple\u2010negative breast cancer (TNBC) cell lines, highlighting the potential for targeting these matrix interfaces in therapeutic approaches. Using a biomimetic collagen\u00a0I interface model, we compared the different breast cancer cell lines, namely, MDA\u2010MB\u2010231, SUM159PT, and Hs578T, during the transmigration process. The interface\u2010induced trigger of invasiveness was more pronounced in MDA\u2010MB\u2010231 and SUM159PT cells. RNA sequencing revealed shared transcriptional response in all three cell lines, with 228 commonly regulated genes and enrichment of pathways linked to cell cycle, chromatin organization, and DNA repair. Differences in pathway activation reflected the baseline characteristics of the three cell lines. Together, the results demonstrate that the topological and mechanical stimuli of tissue interfaces in general induce transcriptional reprogramming in TNBC cells with features of higher aggressiveness.<\/jats:p>","DOI":"10.1002\/adhm.202505616","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:24:35Z","timestamp":1772972675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Common Signatures of Altered Gene Regulation and Invasiveness of Different Breast Cancer Cell Lines after Matrix Interface Crossing"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1089-1744","authenticated-orcid":false,"given":"Cornelia","family":"Clemens","sequence":"first","affiliation":[{"name":"Institute of Biochemistry Leipzig University  Leipzig 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