Engrailed‐1 Promotes Pancreatic Cancer Metastasis
Source abstract
Abstract
Abstract Engrailed‐1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties. Gain‐ and loss‐of‐function experiments demonstrated that EN1 promoted PDA transformation and metastasis in vitro and in vivo. The findings nominate the targeting of EN1 and downstream pathways in aggressive PDA.
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Research context
OpenAlex topics: Cancer Cells and Metastasis · Epigenetics and DNA Methylation · Developmental Biology and Gene Regulation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USA
Comprehensive Cancer Center University of California Davis Sacramento CA 95817 USA
Department of Biochemistry Yonsei University Seoul 03722 South Korea
Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
Lustgarten Foundation Pancreatic Cancer Research Laboratory Cold Spring Harbor NY 11724 USA
Nancy E. and Peter C. Meinig School of Biomedical Engineering Cornell University Ithaca NY 14853 USA
Department of Medicine University of Nebraska Medical Center Omaha NE 68198 USA
Department of Pathology School of Medicine University of California Davis Sacramento CA 95817 USA
Funding
National Research Foundation of Korea · National Institutes of Health · Simons Foundation · National Institute of Environmental Health Sciences · National Cancer Institute
References (85)
Show source-provided references
1. 10.3322/caac.2176310.3322/caac.21763 ↗
2. 10.1146/annurev.pathmechdis.3.121806.15430510.1146/annurev.pathmechdis.3.121806.154305 ↗
3. 10.1038/nature0951510.1038/nature09515 ↗
4. 10.3390/biom1108108210.3390/biom11081082 ↗
5. 10.1016/j.celrep.2018.10.05110.1016/j.celrep.2018.10.051 ↗
6. 10.1016/j.cell.2014.12.02110.1016/j.cell.2014.12.021 ↗
7. 10.1016/j.ccr.2005.04.02310.1016/j.ccr.2005.04.023 ↗
8. 10.1016/j.cell.2017.07.00710.1016/j.cell.2017.07.007 ↗
9. 10.1038/nrc194710.1038/nrc1947 ↗
10. 10.1038/sj.cdd.440170710.1038/sj.cdd.4401707 ↗
11. 10.1038/nature1154710.1038/nature11547 ↗
12. 10.1242/dev.0112810.1242/dev.01128 ↗
13. 10.1523/JNEUROSCI.21-09-03126.200110.1523/JNEUROSCI.21-09-03126.2001 ↗
14. 10.1007/s00441-004-0973-810.1007/s00441-004-0973-8 ↗
15. 10.1016/S0960-9822(02)00645-010.1016/S0960-9822(02)00645-0 ↗
16. 10.1016/j.febslet.2013.01.05410.1016/j.febslet.2013.01.054 ↗
17. 10.18632/oncotarget.2364110.18632/oncotarget.23641 ↗
18. 10.1038/onc.2013.42210.1038/onc.2013.422 ↗
19. Qin G. · J Oncol · 2020 · 2020
20. 10.1007/s10549-021-06328-y10.1007/s10549-021-06328-y ↗
21. 10.3390/ijms2303112310.3390/ijms23031123 ↗
22. 10.1080/15384047.2018.142391310.1080/15384047.2018.1423913 ↗
23. 10.1158/0008-5472.CAN-18-326410.1158/0008-5472.CAN-18-3264 ↗
24. 10.1101/cshperspect.a02610410.1101/cshperspect.a026104 ↗
25. 10.1084/jem.2019238910.1084/jem.20192389 ↗
26. 10.1038/ng.339810.1038/ng.3398 ↗
27. 10.1038/s41467-020-17150-310.1038/s41467-020-17150-3 ↗
28. 10.1038/s41422-019-0195-y10.1038/s41422-019-0195-y ↗
29. 10.1158/2159-8290.CD-18-034910.1158/2159-8290.CD-18-0349 ↗
30. 10.15252/emmm.20160697510.15252/emmm.201606975 ↗
31. 10.1016/j.ccell.2017.07.00710.1016/j.ccell.2017.07.007 ↗
32. 10.1038/nature1696510.1038/nature16965 ↗
33. 10.1126/sciadv.aav678910.1126/sciadv.aav6789 ↗
34. 10.1016/j.ccell.2017.07.00710.1016/j.ccell.2017.07.007 ↗
35. 10.1053/j.gastro.2018.08.03310.1053/j.gastro.2018.08.033 ↗
36. 10.1158/0008-5472.CAN-15-284110.1158/0008-5472.CAN-15-2841 ↗
37. 10.3389/fgene.2018.0010810.3389/fgene.2018.00108 ↗
38. 10.18632/oncotarget.1024210.18632/oncotarget.10242 ↗
39. 10.1002/cam4.77210.1002/cam4.772 ↗
40. 10.3390/ijms2107234610.3390/ijms21072346 ↗
41. 10.3390/ijms2113463810.3390/ijms21134638 ↗
42. 10.3389/fnmol.2019.0007610.3389/fnmol.2019.00076 ↗
43. 10.1186/s40364-018-0122-210.1186/s40364-018-0122-2 ↗
44. 10.1158/0008-5472.CAN-20-067210.1158/0008-5472.CAN-20-0672 ↗
45. 10.1158/2159-8290.CD-21-105910.1158/2159-8290.CD-21-1059 ↗
46. 10.1093/narcan/zcab02310.1093/narcan/zcab023 ↗
47. 10.1053/j.gastro.2023.02.04910.1053/j.gastro.2023.02.049 ↗
48. 10.1056/NEJMoa101192310.1056/NEJMoa1011923 ↗
49. 10.1056/NEJMoa130436910.1056/NEJMoa1304369 ↗
50. 10.1038/s41568-019-0196-710.1038/s41568-019-0196-7 ↗
51. 10.1093/emboj/17.13.370410.1093/emboj/17.13.3704 ↗
52. 10.1128/MCB.18.5.280410.1128/MCB.18.5.2804 ↗
53. 10.1016/j.molcel.2020.04.03410.1016/j.molcel.2020.04.034 ↗
54. 10.1371/journal.pone.008498210.1371/journal.pone.0084982 ↗
55. 10.1016/j.ygeno.2022.11042810.1016/j.ygeno.2022.110428 ↗
56. 10.1038/s41418-019-0473-810.1038/s41418-019-0473-8 ↗
57. 10.1016/j.sjbs.2017.09.01510.1016/j.sjbs.2017.09.015 ↗
58. 10.1242/dev.104.2.30510.1242/dev.104.2.305 ↗
59. 10.1016/0896-6273(94)90024-810.1016/0896-6273(94)90024-8 ↗
60. 10.1006/mcne.1996.000410.1006/mcne.1996.0004 ↗
61. 10.1242/dev.126.19.420110.1242/dev.126.19.4201 ↗
62. 10.1523/JNEUROSCI.22-03-00832.200210.1523/JNEUROSCI.22-03-00832.2002 ↗
63. 10.1038/nn.291610.1038/nn.2916 ↗
64. 10.1038/s41588-022-01134-810.1038/s41588-022-01134-8 ↗
65. 10.1016/S1535-6108(03)00309-X10.1016/S1535-6108(03)00309-X ↗
66. 10.1242/dev.00062010.1242/dev.000620 ↗
67. 10.1002/path.465110.1002/path.4651 ↗
68. 10.1186/gb-2009-10-3-r2510.1186/gb-2009-10-3-r25 ↗
69. 10.1093/bioinformatics/btp35210.1093/bioinformatics/btp352 ↗
70. 10.1093/nar/gkw25710.1093/nar/gkw257 ↗
71. 10.1186/gb-2008-9-9-r13710.1186/gb-2008-9-9-r137 ↗
72. 10.1038/nprot.2012.10110.1038/nprot.2012.101 ↗
73. 10.1093/bioinformatics/btv14510.1093/bioinformatics/btv145 ↗
74. 10.1038/nmeth.331710.1038/nmeth.3317 ↗
75. 10.1093/bioinformatics/btt65610.1093/bioinformatics/btt656 ↗
76. 10.1186/s13059-014-0550-810.1186/s13059-014-0550-8 ↗
77. 10.1038/ng118010.1038/ng1180 ↗
78. 10.1073/pnas.050658010210.1073/pnas.0506580102 ↗
79. 10.1371/journal.pcbi.101037810.1371/journal.pcbi.1010378 ↗
80. 10.1093/nar/gkm41510.1093/nar/gkm415 ↗
81. 10.1093/nar/gkac19410.1093/nar/gkac194 ↗
82. 10.1371/journal.pone.009244410.1371/journal.pone.0092444 ↗
83. 10.1371/journal.pone.014846910.1371/journal.pone.0148469 ↗
84. 10.4161/cam.3622410.4161/cam.36224 ↗
85. 10.1073/pnas.122152611010.1073/pnas.1221526110 ↗