C1orf106 (INAVA) Is a SMAD3-Dependent TGF-β Target Gene That Promotes Clonogenicity and Correlates with Poor Prognosis in Breast Cancer

TL;DR

This study identifies C1orf106 as a gene activated by TGF-β in breast cancer, which promotes tumor growth and is linked to poor outcomes.

Contribution

The novel finding is that C1orf106 is a SMAD3-dependent TGF-β target gene that promotes breast cancer progression.

Findings

C1orf106 is induced by TGF-β in a SMAD3-dependent manner in breast cancer cell lines.

High C1orf106 expression correlates with aggressive tumor traits and poor prognosis in breast cancer.

C1orf106 enhances migration, invasion, and clonogenicity in breast cancer cells.

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.

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