High Atlastin 2-2 (ATL2-2) Expression Associates with Worse Prognosis in Estrogen-Receptor-Positive Breast Cancer

• Published in: Genes
• Main Authors: Reynisdóttir, Inga, Arason, Aðalgeir, Freysteinsdóttir, Edda Sigríður, Kristjánsdóttir, Sigrún Bærings, Hilmarsdóttir, Bylgja, Traustadóttir, Gunnhildur Ásta, Jóhannsson, Óskar Þór, Agnarsson, Bjarni Agnar, Barkardóttir, Rósa Björk
• Other Authors: Other departments, Faculty of Medicine, Landspitali - The National University Hospital of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2023
• Subjects: Náttúrufræðingar; Meinafræði; Krabbameinslæknisfræði; ATL2; ATL2-2; Atlastin 2; breast cancer; endoplasmic reticulum; survival; Prognosis; Humans; Estrogens; Animals; Breast; Female; Mice; Breast Neoplasms/genetics; RNA; Messenger; Genetics; Genetics (clinical); Iceland
• Online Access: https://hdl.handle.net/20.500.11815/4494; https://doi.org/10.3390/genes14081559

Funding Information: This research was funded by a grant to IR and RBB from The Scientific Fund of Landspitali—The National University Hospital in Iceland (grant number A-2021-023). Publisher Copyright: © 2023 by the authors. The disruption of endoplasmic reticulum (ER) homeostasis occurs in many human diseases. Atlastins (ATLs) maintain the branched network of the ER. The dysregulation of ATL2, located at ER network junctions, has been associated with cancer. ATL2 is necessary for lipid droplet formation in murine breast tissue. Thus, we analyzed whether ATL2 has a role in human breast cancer (BC) pathology. The expression of ATL2 variant ATL2-2 was analyzed in breast tumors from the BC cohorts of the TCGA, METABRIC, and two independent Icelandic cohorts, Cohort 1 and 2; its association with clinical, pathological, survival, and cellular pathways was explored. ATL2-2 mRNA and protein expression were higher in breast tumors than in normal tissue. ATL2-2 mRNA associated with tumor characteristics that indicate a worse prognosis. In METABRIC, high ATL2-2 mRNA levels were associated with shorter BC-specific survival (BCSS) in patients with estrogen-receptor-positive luminal breast tumors, which remained significant after correction for grade and tumor size (HR 1.334, CI 1.063–1.673). Tumors with high ATL2 mRNA showed an upregulation of hallmark pathways MYC targets v1, E2F targets, and G2M checkpoint genes. Taken together, the results suggest that high levels of ATL2-2 may support BC progression through key cancer driver pathways. Peer reviewed