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C1orf106 (INAVA) Is a SMAD3-Dependent TGF-β Target Gene That Promotes Clonogenicity and Correlates with Poor Prognosis in Breast Cancer
by Lauren S. Strathearn 1,2,†,Lindsay C. Spender 1,3ORCID,Christina Schoenherr 2ORCID,Susan Mason 2,Ruaridh Edwards 1ORCID,Karen Blyth 2ORCID andGareth J. Inman 1,2,4,*ORCID
1
Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee DD1 4HN, UK
2
Cancer Research UK Scotland Institute, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
3
Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee DD1 4HN, UK
4
Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK
*
Author to whom correspondence should be addressed.
†
Current address: Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Cells 2024, 13(18), 1530; https://doi.org/10.3390/cells13181530
Submission received: 23 February 2024 / Revised: 2 September 2024 / Accepted: 5 September 2024 / Published: 12 September 2024
(This article belongs to the Section Cell Signaling)
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Abstract
Transforming Growth Factor-β (TGF-β) can have both tumour-promoting and tumour-suppressing activity in breast cancer. Elucidating the key downstream mediators of pro-tumorigenic TGF-β signalling in this context could potentially give rise to new therapeutic opportunities and/or identify biomarkers for anti-TGF-β directed therapy. Here, we identify C1orf106 (also known as innate immunity activator INAVA) as a novel TGF-β target gene which is induced in a SMAD3-dependent but SMAD2/SMAD4-independent manner in human and murine cell lines. C1orf106 expression positively correlates with tumourigenic or metastatic potential in human and murine breast cancer cell line models, respectively, and is required for enhanced migration and invasion in response to TGF-β stimulation. C1orf106 promoted self-renewal and colony formation in vitro and may promote tumour-initiating frequency in vivo. High C1orf106 mRNA expression correlates with markers of aggressiveness and poor prognosis in human breast cancer. Taken together, our findings indicate that C1orf106 may act as a tumour promoter in breast cancer.
