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Jeanpierre, S.

Publications and source records attributed to Jeanpierre, S..

2 recordsLinked to original sources

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↗

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↗