From
                    <i>Drosophila</i>
                    to mammals: The evolutionarily conserved homeodomain protein Engrailed affects the antitumor innate immune response

Jieqing Huang; Xiao Lan; Xiaoming Huang; Yuntong Yuan; Mo Liu; Jiyong Liu; Juanjuan Chen; Zhenhui Ye; Ziming Wei; Yuqiang Chen; Zihao Deng; Yuhong Zhang; Yanzhen He; Xiaojing Zhou; Zhenming Cao; Mengyu Jiu; Renjie Jiao; Hua Cai; Jules A. Hoffmann; Di Chen

doi:10.1073/pnas.2603878123

Proceedings of the National Academy of Sciences

From <i>Drosophila</i> to mammals: The evolutionarily conserved homeodomain protein Engrailed affects the antitumor innate immune response

J Jieqing Huang (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) X Xiao Lan (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) X Xiaoming Huang Y Yuntong Yuan (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) M Mo Liu (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) J Jiyong Liu (Department of Chemistry) J Juanjuan Chen (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) Z Zhenhui Ye (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) Z Ziming Wei (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) Y Yuqiang Chen (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) Z Zihao Deng (Department of Chemistry, and the Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction) Y Yuhong Zhang (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) Y Yanzhen He (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) X Xiaojing Zhou (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) Z Zhenming Cao (Zhejiang Key Laboratory of Excited-State Energy Conversion and Energy Storage, Department of Chemistry) M Mengyu Jiu (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) R Renjie Jiao (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) H Hua Cai (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) J Jules A. Hoffmann (Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University) D Di Chen

Abstract

In the process of investigating innate immune reactions against injected oncogenic cells in Drosophila , we noted that the homeodomain protein Engrailed, known since last century for its role in segmentation polarity in embryos, is reactivated in adult males where it considerably restricts the expected proliferation of these cells. Importantly, this effect was not induced following injection of selected pathogens or primary Drosophila embryonic cells. We show that the injection of these cells induces the nuclear translocation of the cytosolic Engrailed protein, and we identify a series of downstream effector genes which are either positively or negatively regulated by this transcription factor. Our results point to unexpected functional parallels between engrailed genes in mammals and flies, which is further illustrated by the phenotypes induced in fly wings and tumor load after ectopic expression of mammalian genes in flies.

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Article Details

Journal Proceedings of the National Academy of Sciences

Volume / Issue Vol. 123, Issue 17

Published April 28, 2026

DOI 10.1073/pnas.2603878123

ISSN 0027-8424

Publisher National Academy of Sciences

Journal Info

Proceedings of the National Academy of Sciences

National Academy of Sciences

ISSN: 0027-8424 Life Sciences