Angiopoietin-1 Upregulates Cancer Cell Motility in Colorectal Cancer Liver Metastases through Actin-Related Protein 2/3

• Published in: Cancers Vol. 14; no. 10; p. 2540
• Main Authors: Rada, Miran, Kapelanski-Lamoureux, Audrey, Tsamchoe, Migmar, Petrillo, Stephanie, Lazaris, Anthoula, Metrakos, Peter
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.05.2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Actin; Actin-related protein 2; AKT protein; Angiogenesis; Angiopoietin; Antibodies; Antigens; Cancer therapies; Colorectal cancer; Colorectal carcinoma; Kinases; Liver; Liver cancer; Metastases; Metastasis; Mortality; Proteins; Therapeutic targets; Tumors; Canada; United States > US; CRCLM; ARP2/3; Tie2; angiogenesis; Ang1; vessel co-option; PI3K/AKT
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14102540

Resistance to anti-angiogenic therapy is a major challenge in the treatment of colorectal cancer liver metastases (CRCLMs). Vessel co-option has been identified as a key contributor to anti-angiogenic therapy resistance in CRCLMs. Recently, we identified a positive correlation between the expression of Angiopoietin1 (Ang1) in the liver and the development of vessel co-opting CRCLM lesions in vivo. However, the mechanisms underlying its stimulation of vessel co-option are unclear. Herein, we demonstrated Ang1 as a positive regulator of actin-related protein 2/3 (ARP2/3) expression in cancer cells, in vitro and in vivo, which is known to be essential for the formation of vessel co-option in CRCLM. Significantly, Ang1-dependent ARP2/3 expression was impaired in the cancer cells upon Tie2 or PI3K/AKT inhibition in vitro. Taken together, our results suggest novel mechanisms by which Ang1 confers the development of vessel co-option in CRCLM, which, targeting this pathway, may serve as promising therapeutic targets to overcome the development of vessel co-option in CRCLM.