Inhibitor of DNA binding-1 is a key regulator of cancer cell vasculogenic mimicry
Date
2025
Authors
Thompson, E.J.
Dorward, E.L.
Jurrius, K.
Nataren, N.
Tondl, M.
Myo Min, K.K.
Cockshell, M.P.
Fouladzadeh, A.
Toubia, J.
Denichilo, M.
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Journal article
Citation
Molecular Oncology, online, 2025; online(9):1-20
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Abstract
Solid tumours routinely access the blood supply by promoting endothelium-dependent angiogenesis; but tumour vasculature can also be formed by cancer cells themselves via vasculogenic mimicry (VM). Investigation of the gene expression profile during the early stages of VM formation by MDA-MB-231-LM2 breast cancer cells identified the transcriptional regulator inhibitor of DNA binding 1 (ID1) to be elevated similar to 10-fold within the first 2 hours. This role for ID1 in promoting VM was supported by ID1 genetic knockdown or chemical inhibition interrupting VM formation by MDA-MB-231-LM2 (breast) and BxPC-3 (pancreatic) cancer cells. More specifically, reducing ID1 lowered cancer cell expression of endothelial cell genes (e.g. CDH5, TIE2) and production of pro-angiogenic proteins (e.g. VEGF, CD31, MMP9 and IL-8). In silico analysis of MDA-MB-231 cells engrafted into mice identified elevated ID1 expression in cancer cells that had metastasised to the lungs or liver, and an enrichment of pro-angiogenic genes. Additionally, Id1 knockdown in 4T1.13 murine breast cancer cells demonstrated reduced tumour growth and metastasis in vivo. Taken together, this study further implicates ID1 in a vascular program within cancer cells that supports disease progression.
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Data source: supporting information, https://doi.org/10.1002/1878-0261.70027
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Copyright 2025 The Authors. (http://creativecommons.org/licenses/by/4.0/)
Access Condition Notes: This is an open access article under the terms of the Creative Commons Attribution License, which permits use,distribution and reproduction in any medium, provided the original work is properly cited.