Biology subjects

Recouvreux, M. S.

Publications and source records attributed to Recouvreux, M. S..

4 recordsLinked to original sources

bioRxiv2026

Spatially resolved transcriptional programs link fallopian tube precursor lesions to immune activation and stromal reorganization

Despite its name, high-grade serous ovarian carcinoma (HGSC) originates in the fallopian tube, not the ovary, arising from a morphologically recognizable precursor lesion, serous tubal intraepithelial carcinoma (STIC). Yet the early cellular and microenvironmental changes driving this transformation remain poorly understood, limiting progress in early detection, interception, and prevention. Here, we generated a Visium HD spatial transcriptomic atlas of fallopian tube carcinogenesis spanning histologically unremarkable fallopian tube epithelium (FTE), STIC, and invasive HGSC. This approach enabled unbiased, tissue-wide, whole-transcriptome mapping at single-cell-level resolution within preserved histologic architecture, providing spatial granularity beyond prior region-of-interest-based platforms. STIC lesions displayed a coordinated epithelial transformation program marked by proliferation, replication stress, DNA repair activation, chromatin remodeling, and induction of tumor-associated antigens, including PRAME and CLDN6, which are emerging targets for vaccine and antigen-directed therapeutic strategies. In contrast, histologically unremarkable FTE contained spatially restricted epithelial defense programs marked by SCGB1A1 and MUC6, suggesting localized protective states that may influence susceptibility to malignant transformation. Using distance- and density-aware spatial analyses, we found that precursor lesions were embedded within immune-enriched, stromal-depleted microenvironments characterized by interferon-dominant immune activation, attenuation of TNF/NF-{kappa}B signaling, macrophage and lymphoid remodeling, and extracellular matrix-associated fibroblast interactions. Computational pathology analysis of collagen architecture confirmed reduced collagen fiber density in STIC-adjacent stroma, linking transcriptomic evidence of stromal remodeling to structural extracellular matrix changes. Together, these data define early epithelial, immune, and stromal programs associated with STIC and identify tumor-associated antigens, epithelial defense states, and immune-stromal niches as candidate targets for HGSC prevention and early interception.

cancer biology↗

bioRxiv2026

Deformability screening identifies NUDT5 as a mediator of cellular mechanobiology

How cells deform, sense, and respond to mechanical cues drives physiological and disease processes ranging from development to cancer metastasis; however, unbiased approaches to identify mechanical mediators are lacking. We screened 1280 compounds to identify modulators of cancer cell deformability using a cellular filtration assay and identified 92 compounds that significantly reduced deformability of ovarian cancer cells; top hits also reduced migration and invasion. Connectivity mapping of the top 21 compounds identified NUDT5 (Nudix hydrolase 5) as a predicted mechanical mediator; transcriptomic analyses implicated NUDT5 in mechanobiology and metabolic processes. We confirmed that NUDT5 mediates intracellular ATP and cellular mechanical behaviors, including morphology and deformability. In ovarian cancer, increased NUDT5 levels were associated with higher tumor stage and worse patient survival; NUDT5 inhibition reduced migration and colony formation in vitro and peritoneal tumor burden in mice. These findings establish deformability-based screening as a platform for discovering mechanical mediators and identify NUDT5 as a therapeutic target in ovarian cancer. TeaserScreening cells based on deformability provides an unbiased approach to identify NUDT5 as a mediator of cell mechanics

cell biology↗

bioRxiv2024

Ablation of hematopoietic stem cell derived adipocytes reduces tumor burden in syngeneic mouse models of high-grade serous carcinoma

Hematopoietic stem cell-derived adipocytes (HSCDAs) are an adipose subtype derived from myeloid precursors that are distinct from conventional mesenchymal adipocytes (CMAs). We hypothesized that HSCDAs promote high grade serous carcinoma (HGSC), the most common form of ovarian cancer. Despite similar rates of differentiation, primary human HSCDAs from female donors showed marked transcriptional differences from CMAs, including downregulation of cell cycle and upregulation of lipid metabolic pathways. HSCDAs secreted greater amounts of inflammatory cytokines than CMAs. We also conducted two independent tumor studies using ID8 and SO syngeneic HGSC murine models in immunocompetent mice that were either HSCDA Proficient (HSCDA-Pro; can make both adipocyte subtypes) or Deficient (HSCDA-Def; can only make CMAs). Tumor burden trended lower in HSCDA-Def mice in both models. Relative to HSCDA-Pro mice, omental ID8 tumors from HSCDA-Def mice downregulated transcription of multiple metabolic pathways that were enriched in human HSCDA cells in vitro, suggesting that ablation of HSCDAs altered the tumor metabolic environment. Compared to HSCDA-Pro mice, tumors from HSCDA-Def mice had lower densities of dendritic cells (DC) and natural killer (NK) cells, as well as fewer DCs, NKs, and B-cells in proximity to tumor cells. Our data suggest that HSCDAs alter the peritoneal immune and metabolic environment to support HGSC progression. ONE SENTENCE SUMMARYHematopoietic stem cell derived adipocytes may alter the peritoneal metabolic and immune environment to establish a metastatic niche and support ovarian cancer progression.

cancer biology↗

bioRxiv2022

RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer.

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. Androgen receptor (AR) is expressed in up to 50% of TNBC, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to RUNX1 regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in HCI-009 patient-derived xenograft (PDX) tumors (p<0.05). RUNX1 is increased in a CSC-like experimental model in MDA-MB-453 and SUM-159PT cells (p<0.05). Inhibition of RUNX1 transcriptional activity reduced the expression of CSC markers. Interestingly, RUNX1 inhibition reduced cell viability and enhanced paclitaxel and enzalutamide sensitivity. Targeting RUNX1 may be an attractive strategy to potentiate the anti-tumor effects of AR inhibition, specifically in the slow growing CSC-like populations that resist chemotherapy leading to metastatic disease.

cancer biology↗