Biology subjects

Treilleux, I.

Publications and source records attributed to Treilleux, I..

3 recordsLinked to original sources

bioRxiv2025

The BMP4-BMPR1A axis represses BRCA1, inducing BRCAness in mammary stem cells and contributing to tumor initiation in basal-like breast cancer

Basal-like breast cancer (BLBC) is an aggressive subtype frequently characterized by homologous recombination deficiency (HRD) and BRCAness, even in the absence of BRCA1 mutations. Here, we identify the BMP4-BMPR1A signaling axis as a novel regulator of BRCA1 expression and a driver of BRCAness in non-transformed immature mammary cells. We observed that high BMPR1A expression is correlated with low BRCA1 levels and poor BLBC prognosis in patients. We show that exposure to BMP4 induces BRCA1 transcriptional repression via BMPR1A, promoting a basal differentiation and impairing homologous recombination. This results in increased sensitivity to PARP inhibitors (PARPi) and accumulation of genetically-unstable, immature cells. In addition, long-term BMP4 stimulation or BMPR1A overexpression induced transformation. Our findings uncover a mechanism by which the tumor microenvironment may contribute to BLBC initiation through BMP4-induced suppression of BRCA1, and highlight BMP signaling and the resulting BRCAness as a therapeutic vulnerability in wild-type BRCA1 BLBCs.

cancer biology↗

bioRxiv2023

IL-33 drives polyfunctionality and antitumor activity of a unique ST2+ NK cell population

Despite increasing recognition of NK cell diversity, their functional heterogeneity and its relevance to cancer remain incompletely understood. Here, we show that IL-12 promotes the emergence of a distinct ST2/IL33R+ NK cell state poised for robust activation by IL-33. Human ST2 NK cells exhibit a unique transcriptional program, an intermediate differentiation state between CD56bright and CD56dim NK cells, and enhanced polyfunctionality combining proliferation, cytokine production, and cytotoxicity. ST2 NK cells were identified across human and murine tumor datasets. In murine breast cancer models, IL-33 and IL-12 cooperated to elicit potent antitumor responses dependent on IFN-{gamma} and ST2 NK cells. In cancer patients, IL-12 unleashed tumor-infiltrating ST2 NK cells' potential to produce IFN-g in response to IL-33, an IL33hi-NKhi score was associated with prolonged survival, and ST2 NK cells correlated with improved immunotherapy response. Collectively, these findings identify ST2 NK cells as a therapeutically actionable NK cell state promoting antitumor immunity.

cancer biology↗

bioRxiv2018

A Gender-Dependent Molecular Switch of Inflammation via MyD88/Estrogen Receptor-alpha Interaction

Most Toll-like receptors and IL-1/IL-18 receptors activate a signaling cascade via the adaptor molecule MyD88, resulting in NF-{kappa}B activation and inflammatory cytokine and chemokine production. Females are less susceptible than males to inflammatory conditions, presumably due to protection by estrogen. Here we show that MyD88 interacts with a methylated, cytoplasmic form of estrogen receptor-alpha (methER-). This interaction is required for NF-{kappa}B transcriptional activity and pro-inflammatory cytokine production, and is dissociated by estrogen. Importantly, we show a strong gender segregation in gametogenic reproductive organs, with MyD88/methER- interactions found in testicular tissues and in ovarian tissues from menopausal women, but not in ovaries from women age 49 and less -suggesting a role for estrogen in disrupting this complex in situ. Collectively, our results indicate that the formation of MyD88/methER- complexes during inflammatory signaling and their disruption by estrogen may represent a mechanism that contributes to gender bias in inflammatory responses.

immunology↗