Kshitiz Afzal, Junaid Maziarz, Jamie D. Hamidzadeh, Archer Liang, Cong Erkenbrack, Eric M. Kim, Hong Nam Haeger, Jan-Dirk Pfarrer, Christiane Hoang, Thomas Ott, Troy Spencer, Thomas Pavlicev, Mihaela Antczak, Douglas F. Levchenko, Andre Wagner, Gunter P. 2024-01-19T18:33:25Z 2024-01-19T18:33:25Z 2021-09-05 2019-12 2397-334X https://pubs.kist.re.kr/handle/201004/119249 Among mammals, placental invasion is correlated with vulnerability to malignancy. Animals with more invasive placentation (for example, humans) are more vulnerable to malignancy. To explain this correlation, we propose the hypothesis of 'Evolved Levels of Invasibility' proposing that the evolution of invasibility of stromal tissue affects both placental and cancer invasion. We provide evidence for this using an in vitro model. We find that bovine endometrial and skin fibroblasts are more resistant to invasion than are their human counterparts. Gene expression profiling identified genes with high expression in human but not in bovine fibroblasts. Knocking down a subset of them in human fibroblasts leads to stronger resistance to cancer cell invasion. Identifying the evolutionary determinants of stromal invasibility can provide important insights to develop rational antimetastatic therapeutics. English NATURE RESEARCH TGF-BETA GENE-EXPRESSION PPAR-GAMMA COLLECTIVE INVASION TUMOR-STROMA CELL RESISTANCE WNT TUMORIGENESIS FIBROBLASTS Evolution of placental invasion and cancer metastasis are causally linked Article 10.1038/s41559-019-1046-4 1 NATURE ECOLOGY & EVOLUTION, v.3, no.12, pp.1743 - + NATURE ECOLOGY & EVOLUTION 3 12 1743 + scie scopus 000500728800024 2-s2.0-85075450087 Ecology Evolutionary Biology Environmental Sciences & Ecology Evolutionary Biology Article TGF-BETA GENE-EXPRESSION PPAR-GAMMA COLLECTIVE INVASION TUMOR-STROMA CELL RESISTANCE WNT TUMORIGENESIS FIBROBLASTS