Drain, A. | bioRxiv Science

bioRxiv2025

NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer

Metastatic progression depends upon the ability of disseminated tumor cells to evade immune surveillance. MHC molecule expression facilitates T cell recognition and activation to permit the eradication of metastatic tumor cells. We identified nuclear corepressor 2 (NCOR2) as a key epigenetic regulator of MHC class I molecule expression on breast tumor cells. Patients with triple negative breast cancers (TNBC) that expressed high levels of NCOR2 also exhibited reduced metastasis free survival and decreased MHC class I expression, and the metastatic lesions in patients with TNBC had high nuclear NCOR2 and reduced CD8 T cell levels and activity. Genetically and experimentally reducing NCOR2 expression in tumor cells permitted interferon gamma upregulation of MHC class I, and potentiated CD8 T cell activity and induction of apoptosis to repress metastatic progression of disseminated breast cancer cells. These studies provide evidence to support NCOR2 as a targetable epigenetic regulator of metastasis towards which therapies could be developed to reduce patient mortality.

cancer biology↗

bioRxiv2019

Medicago truncatula possesses a single Shaker outward K+ channel: functional characterization and roles in planta

The model legume Medicago truncatula possesses a single outward Shaker K+ channel, while Arabidopsis thaliana possesses two channels of this type, named SKOR and GORK, the former having been shown to play a major role in K+ secretion into the xylem sap in the root vasculature and the latter to mediate the efflux of K+ across the guard cell membrane upon stomatal closure. Here we show that the expression pattern of the single M. truncatula outward Shaker channel, which has been named MtGORK, includes the root vasculature, guard cells and root hairs. As shown by patch-clamp experiments on root hair protoplasts, besides the Shaker-type slowly-activating outwardly-rectifying K+ conductance encoded by MtGORK, a second K+-permeable conductance, displaying fast activation and weak rectification, can be expressed by M. truncatula. A KO mutation resulting in absence of MtGORK activity is shown to weakly reduce K+ translocation to shoots, and only in plants engaged in rhizobial symbiosis, but to strongly affect the control of stomatal aperture and transpitational water loss. In legumes, the early electrical signaling pathway triggered by Nod Factor perception is known to comprise a short transient depolarization of the root hair plasma membrane. In absence of MtGORK functional expression, while the rate of the membrane repolarization is shown to be decreased by about 3 times, this defect is without any consequence on infection thread development and nodule production, indicating that the plant capacity to engage rhizobial symbiosis does not require integrity of the early electrical signaling events.

plant biology↗