Biology subjects

Guyot, B.

Publications and source records attributed to Guyot, B..

3 recordsLinked to original sources

bioRxiv2026

Chronic Exposure to Nanoplastics Alters Stem Cell Type-Specific Mechanisms, Promoting Cancer Development

Increasing levels of nanoplastics (NPLs) in the environment raise concerns about their effects on human health. We investigated the impact of the most prevalent NPLs, namely polyethylene terephthalate (PET) and polystyrene (PS), on stem cells (SCs), which persist for decades, support tissue function, and are often implicated in cancer development. Long-term exposure to both NPLs similarly affected mammary SC features with an enhanced self-renewal and altered 3D organization, without impairing differentiation capacity. Moreover, both NPLs significantly increased invasiveness and anchorage-independent growth, albeit molecular profiling revealed distinct signatures and mechanisms, indicating a shift towards a more aggressive phenotype. NPLs also synergized with BMP2 signaling, known to be disrupted by pollutants. These findings highlight how NPLs may contribute to early pre-neoplastic changes through distinct and cooperative mechanisms.

cancer biology↗

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↗

bioRxiv2020

Development of a soft cell confiner to decipher the impact of mechanical stimuli on cells

Emerging evidence suggests the importance of mechanical stimuli in normal and pathological situations for the control of many critical cellular functions. While the effect of matrix stiffness has been and is still extensively studied, few studies have focused on the role of mechanical stresses. The main limitation of such analyses is the lack of standard in vitro assays enabling extended mechanical stimulation compatible with dynamic biological and biophysical cell characterization. We have developed an agarose-based microsystem, the soft cell confiner, which enables the precise control of confinement for single or mixed cell populations. The rigidity of the confiner matches physiological conditions and enables passive medium renewal. It is compatible with time-lapse microscopy, in situ immunostaining, and standard molecular analyses, and can be used with both adherent and non-adherent cell lines. Cell proliferation of various cell lines (hematopoietic cells, MCF10A epithelial breast cells and HS27A stromal cells) was followed for several days up to confluence using video-microscopy and further documented by Western blot and immunostaining. Interestingly, even though the nuclear projected area was much larger upon confinement, with many highly deformed nuclei (non-circular shape), cell viability, assessed by live and dead cell staining, was unaffected for up to 8 days in the confiner. However, there was a decrease in cell proliferation upon confinement for all tested cell lines. The soft cell confiner is thus a valuable tool to decipher the effect of long-term confinement and deformation on the biology of cell populations. This tool will be instrumental in deciphering the impact of nuclear and cytoskeletal mechanosensitivity in normal and pathological conditions involving highly confined situations, such as those reported upon aging with fibrosis or during cancer. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY A unique tool to analyze the role of long-term effect of mechanical confinement in normal and pathological conditions

biophysics↗