Research
Invasion I: Cohesive Clusters
Successful metastasis relies on cohesive clusters of tumor cells. The image on the right shows three distinct clusters of human adenocarcinoma within the same patient sample directly revealing molecular heterogeneity. Immuno-histochemistry of five distinct haptens were detected: ER (QD 585, red), Ki-67 (QD 605, light blue), PR (QD 625, blue), p53 (QD 655, yellow), and Her2 (QD 705, green).
Recent studies in cell biology and informatics, combined with mass spectrometry, suggest that the integrin adhesome network explains how cohesive tumor cell clusters invade muscle and nerve microenvironments while resisting adhesion-dependent therapies. Targeting these clusters leverages ECM adhesion’s role in promoting tumor survival, potentially preventing drug and radiotherapy resistance.
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Marr KD, Gard JMC, Harryman WL, Keeswood EJ, Paxson AI, Wolgemuth C, Knudsen BS, Nagle RB, Hazlehurst L, Sorbellini M, Cress AE. Biophysical phenotype mixtures reveal advantages for tumor muscle invasion in vivo. Biophys J. 2023 Nov 7;122(21):4194-4206. doi: 10.1016/j.bpj.2023.09.016. Epub 2023 Sep 26. PMID: 37766428; PMCID: PMC10645557.
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Harryman WL, Marr KD, Nagle RB, Cress AE. Integrins and Epithelial-Mesenchymal Cooperation in the Tumor Microenvironment of Muscle-Invasive Lethal Cancers. Front Cell Dev Biol. 2022 Mar 1;10:837585. doi: 10.3389/fcell.2022.837585. PMID: 35300411; PMCID: PMC8921537.
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Rubenstein CS, Gard JMC, Wang M, McGrath JE, Ingabire N, Hinton JP, Marr KD, Simpson SJ, Nagle RB, Miranti CK, Warfel NA, Garcia JGN, Arif-Tiwari H, Cress AE. Gene Editing of α6 Integrin Inhibits Muscle Invasive Networks and Increases Cell-Cell Biophysical Properties in Prostate Cancer. Cancer Res. 2019 Sep 15;79(18):4703-4714. doi: 10.1158/0008-5472.CAN-19-0868. Epub 2019 Jul 23. PMID: 31337652; PMCID: PMC6750953.
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Wang M, Hinton JP, Gard JMC, Garcia JGN, Knudsen BS, Nagle RB, Cress AE. Integrin α6β4E variant is associated with actin and CD9 structures and modifies the biophysical properties of cell-cell and cell-extracellular matrix interactions. Mol Biol Cell. 2019 Mar 21;30(7):838-850. doi: 10.1091/mbc.E18-10-0652. Epub 2019 Mar 13. PMID: 30865564; PMCID: PMC6589785.
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Das L, Gard JMC, Prekeris R, Nagle RB, Morrissey C, Knudsen BS, Miranti CK, Cress AE. Novel Regulation of Integrin Trafficking by Rab11-FIP5 in Aggressive Prostate Cancer. Mol Cancer Res. 2018 Aug;16(8):1319-1331. doi: 10.1158/1541-7786.MCR-17-0589. Epub 2018 May 14. PMID: 29759989; PMCID: PMC6369592.
