@article{8b204827919c4a609e23f711f67c6069,
title = "Collective invasion in breast cancer requires a conserved basal epithelial program",
abstract = "Carcinomas typically invade as a cohesive multicellular unit, a process termed collective invasion. It remains unclear how different subpopulations of cancer cells contribute to this process. We developed three-dimensional (3D) organoid assays to identify the most invasive cancer cells in primary breast tumors. Collective invasion was led by specialized cancer cells that were defined by their expression of basal epithelial genes, such as cytokeratin-14 (K14) and p63. Furthermore, K14+ cells led collective invasion in the major human breast cancer subtypes. Importantly, luminal cancer cells were observed to convert phenotypically to invasive leaders following induction of basal epithelial genes. Although only a minority of cells within luminal tumors expressed basal epithelial genes, knockdown of either K14 or p63 was sufficient to block collective invasion. Our data reveal that heterotypic interactions between epithelial subpopulations are critical to collective invasion. We suggest that targeting the basal invasive program could limit metastatic progression.",
author = "Cheung, {Kevin J.} and Edward Gabrielson and Zena Werb and Ewald, {Andrew J.}",
note = "Funding Information: We thank Koen Schipper, Jen Beck, and Audrey Brenot for technical support. We thank Ellen Tully for performing K14 immunohistochemistry on archival tumors. Human tissue samples were provided by the Johns Hopkins Hospital and by the Cooperative Human Tissue Network, which is funded by the NCI. We also thank William C. Hines, Paul Yaswen, Pedram Argani, and Lisa Jacobs for assistance with acquisition of primary human tumor specimens. We thank Mikala Egeblad, William Matsui, Vered Stearns, Sara Sukumar, Tamara Lotan, and Charles Rudin for scientific discussions. This study was funded by grants from the NCI (R01 CA057621 to Z.W.; U01 CA155758, P50 CA103175, and P50 CA88843 to A.J.E.), the NIEHS (U01 ES019458 to Z.W.), the U.S. Department of Defense (W81XWH-12-1-0018 to K.J.C.), the Mary Kay Foundation (036-13 to A.J.E.), a Safeway Foundation Award for Breast Cancer Research (to A.J.E.), funds from the Avon Foundation for Women (to A.J.E.), funds from the Cindy Rosencrans Fund for Triple Negative Breast Cancer Research (to A.J.E.), and a Research Scholar Grant (RSG-12-141-01-CSM to A.J.E.) from the American Cancer Society. This study benefited from a Zeiss 710 NLO 2-photon microscope (JHUSOM Microscope Facility) purchased through funds from S10RR024550. ",
year = "2013",
month = dec,
day = "19",
doi = "10.1016/j.cell.2013.11.029",
language = "English (US)",
volume = "155",
pages = "1639--1651",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}