PUBLICATION
ROME, an ancient gene with a novel function in vertebrates, is a key modulator of embryonal development and cancer metastasis
- Authors
- Molotkova, A., Deniz, E., Swift, M., Glasgow, E., Ma, J., Petro, J.A., Frye, I., Ozdemirli, M., Pesic, D., Ahern, G.P., Suter, R.K., Tiwari, P.B., Shlien, A., Toretsky, J., Üren, A.
- ID
- ZDB-PUB-260207-6
- Date
- 2026
- Source
- Cancer research communications : (Journal)
- Registered Authors
- Glasgow, Eric, Swift, Matthew Russell
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Movement
- Embryonic Development*/genetics
- Gene Expression Regulation, Neoplastic
- Humans
- Mice
- Neoplasm Metastasis
- Neoplasms*/genetics
- Neoplasms*/metabolism
- Neoplasms*/pathology
- Wnt Signaling Pathway
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 41650465 Full text @ Cancer Res Commun
Citation
Molotkova, A., Deniz, E., Swift, M., Glasgow, E., Ma, J., Petro, J.A., Frye, I., Ozdemirli, M., Pesic, D., Ahern, G.P., Suter, R.K., Tiwari, P.B., Shlien, A., Toretsky, J., Üren, A. (2026) ROME, an ancient gene with a novel function in vertebrates, is a key modulator of embryonal development and cancer metastasis. Cancer research communications. :.
Abstract
INAFM2, the human homolog of the Drosophila inaF, is a predicted membrane protein with no known function in vertebrates. Through an in vivo genome-wide transcriptional activation screen, we uncovered INAFM2 as a potent driver of metastasis, leading us to propose naming the vertebrate gene and its protein product ROME (Regulator of Metastasis). We discovered ROME's subcellular localization, posttranslational modifications, and transcriptional profiles related to its expression. ROME negatively regulates the canonical Wnt pathway by directly binding to beta-catenin. Blocking ROME expression in zebrafish embryos results in severe developmental defects and early mortality, which can be reversed by inhibiting the canonical Wnt pathway. Notably, we demonstrate that ROME expression regulates human cancer cell motility and invasion in vitro and metastasis in vivo in both zebrafish and immunodeficient mice via tail vein and orthotopic injection models. ROME-mediated increase in cancer cell intravasation is dependent on its direct interaction with vimentin. Further, we show that elevated ROME expression correlates with poorer patient survival in multiple human cancers. Taken together, this is the first report of the vertebrate ROME gene producing a biologically active plasma membrane glycoprotein that is critical for normal development and metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping