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The tumor microenvironment plays a critical role in cancer progression. This microenvironment is composed of various cells embedded in the extracellular matrix (ECM). Laminin\u2010111, a major ECM glycoprotein, produces bioactive peptides that influence tumor biology. We have shown that the laminin\u2010derived peptide C16 (KAFDITYVRLKF), located in the short arm of the \u03b31 chain, regulates migration, invasion, and invadopodia formation in different cancer cells. Our findings suggest that the regulatory mechanisms underlying the effects of C16 are associated with \u03b21 integrin. This prompted us to investigate the interaction between the C16 peptide and \u03b21 integrin in breast cancer cells. We found that breast cancer cells bind to C16 peptide, and this attachment is inhibited by \u03b21 integrin depletion via siRNA. Cellular localization of the C16 peptide was analyzed using transmission electron microscopy (TEM) and time\u2010lapse fluorescence microscopy. TEM revealed that nanogold\u2010conjugated C16 decorated the cell membrane and was localized in intracellular vesicles, indicating peptide endocytosis. Time\u2010lapse confocal microscopy showed that C16 was internalized by breast cancer cells within 2\u2009h of incubation, with this process increasing over time. Based on these observations, we hypothesized that the peptide is endocytosed and directed to the endosome\u2010lysosome pathway for degradation. Time\u2010lapse imaging demonstrated that part of the internalized peptide colocalized with lysosomes in breast cancer cells. This suggests that C16 may be involved in integrin recycling. Furthermore, rhodamine\u2010labeled C16 colocalized with activated \u03b21 integrins. Flow cytometry analysis showed that C16 increased \u03b21 integrin activation starting at 1\u2009h of treatment. In summary, our results suggest that after interacting with the cell membrane and activating \u03b21 integrins, breast cancer cells internalize peptide C16, which plays a role in \u03b21 integrin turnover.<\/jats:p>","DOI":"10.1002\/jcp.70157","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T07:11:29Z","timestamp":1774509089000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Laminin\u2010Derived Peptide C16 Interacts With \u03b21 Integrin, and Is Internalized by Vesicles Through Endocytic Pathway"],"prefix":"10.1002","volume":"241","author":[{"given":"Maria Raquel Unterkircher","family":"Galheigo","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 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