PMID- 35986012 OWN - NLM STAT- MEDLINE VI - 13 IP - 1 TI - Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma. PG - 4897 CI - © 2022. The Author(s). LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nat Commun JT - Nature communications JID - 101528555 IS - 2041-1723 (Electronic) LID - 10.1038/s41467-022-32670-w [doi] FAU - Yerly, Laura AU - Yerly L AUID- ORCID: http://orcid.org/0000-0003-2663-8101 AD - Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, 1011, Lausanne, Switzerland. FAU - Pich-Bavastro, Christine AU - Pich-Bavastro C AUID- ORCID: http://orcid.org/0000-0002-6526-749X AD - Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, 1011, Lausanne, Switzerland. FAU - Di Domizio, Jeremy AU - Di Domizio J AUID- ORCID: http://orcid.org/0000-0002-6281-3918 AD - Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, 1011, Lausanne, Switzerland. FAU - Wyss, Tania AU - Wyss T AD - Bioinformatics Core Facility (BCF), Swiss Institute of Bioinformatics, Quartier UniL-Sorge, Bâtiment Amphipole, 1015, Lausanne, Switzerland. FAU - Tissot-Renaud, Stéphanie AU - Tissot-Renaud S AD - Department of Oncology, Immune Landscape Laboratory, Center of Experimental Therapeutics, Lausanne University Hospital Center, 1011, Lausanne, Switzerland. FAU - Cangkrama, Michael AU - Cangkrama M AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, 8093, Zürich, Switzerland. FAU - Gilliet, Michel AU - Gilliet M AUID- ORCID: http://orcid.org/0000-0002-4609-3762 AD - Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, 1011, Lausanne, Switzerland. FAU - Werner, Sabine AU - Werner S AUID- ORCID: http://orcid.org/0000-0001-7397-8710 AD - Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, 8093, Zürich, Switzerland. FAU - Kuonen, François AU - Kuonen F AUID- ORCID: http://orcid.org/0000-0001-6137-7483 AD - Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, 1011, Lausanne, Switzerland. francois.kuonen@chuv.ch. IS - 2041-1723 (Linking) SB - IM MH - *Carcinoma, Basal Cell/pathology MH - Cell Communication MH - Extracellular Matrix/metabolism MH - Fibroblasts/metabolism MH - Humans MH - *Skin Neoplasms/pathology PMC - PMC9391376 DCOM- 20220823 LR - 20221117 DP - 20220820 DEP - 20220820 AB - Tumors invade the surrounding tissues to progress, but the heterogeneity of cell types at the tumor-stroma interface and the complexity of their potential interactions hampered mechanistic insight required for efficient therapeutic targeting. Here, combining single-cell and spatial transcriptomics on human basal cell carcinomas, we define the cellular contributors of tumor progression. In the invasive niche, tumor cells exhibit a collective migration phenotype, characterized by the expression of cell-cell junction complexes. In physical proximity, we identify cancer-associated fibroblasts with extracellular matrix-remodeling features. Tumor cells strongly express the cytokine Activin A, and increased Activin A-induced gene signature is found in adjacent cancer-associated fibroblast subpopulations. Altogether, our data identify the cell populations and their transcriptional reprogramming contributing to the spatial organization of the basal cell carcinoma invasive niche. They also demonstrate the power of integrated spatial and single-cell multi-omics to decipher cancer-specific invasive properties and develop targeted therapies.