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- Title
Runt related transcription factor-1 plays a central role in vessel co-option of colorectal cancer liver metastases.
- Authors
Rada, Miran; Kapelanski-Lamoureux, Audrey; Petrillo, Stephanie; Tabariès, Sébastien; Siegel, Peter; Reynolds, Andrew R.; Lazaris, Anthoula; Metrakos, Peter
- Abstract
Colorectal cancer liver metastasis (CRCLM) has two major histopathological growth patterns: angiogenic desmoplastic and non-angiogenic replacement. The replacement lesions obtain their blood supply through vessel co-option, wherein the cancer cells hijack pre-existing blood vessels of the surrounding liver tissue. Consequentially, anti-angiogenic therapies are less efficacious in CRCLM patients with replacement lesions. However, the mechanisms which drive vessel co-option in the replacement lesions are unknown. Here, we show that Runt Related Transcription Factor-1 (RUNX1) overexpression in the cancer cells of the replacement lesions drives cancer cell motility via ARP2/3 to achieve vessel co-option. Furthermore, overexpression of RUNX1 in the cancer cells is mediated by Transforming Growth Factor Beta-1 (TGFβ1) and thrombospondin 1 (TSP1). Importantly, RUNX1 knockdown impaired the metastatic capability of colorectal cancer cells in vivo and induced the development of angiogenic lesions in liver. Our results confirm that RUNX1 may be a potential target to overcome vessel co-option in CRCLM. Miran Rada et al. identify a key role for RUNX1 in liver metastasis of colorectal cancer. They show that RUNX1 is necessary for driving blood vessel co-option from surrounding liver tissue and that regulation of this process relies on a signaling feedback loop between RUNX1 transcriptional target TSP1 in tumor cells and TGFβ1 in the liver.
- Subjects
TRANSCRIPTION factors; COLORECTAL cancer; LIVER metastasis; HISTOPATHOLOGY; BLOOD vessels
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02481-8