Biology subjects

Berry, W. L.

Publications and source records attributed to Berry, W. L..

2 recordsLinked to original sources

bioRxiv2026

The Ets transcription factor ETV4 regulates FGF1-dependent proliferation and glycolysis in ER-positive breast cancer

Obesity is a risk factor for estrogen receptor (ER) positive breast cancer. Beyond body mass index, adult weight gain increases breast cancer risk. During weight gain, hypertrophic adipocytes produce fibroblast growth factor 1 (FGF1), which drives estrogen-independent growth of ER-positive tumors. Effects of FGF1 on breast cancer cells include elevated proliferation and enhanced glycolytic activity. We identified the Ets transcription factor ETV4 as a target of FGF1 treatment across multiple breast cancer cell lines. Our objective was to define the role of ETV4 in mediating the tumor-promotional effects of FGF1, to better understand how weight gain and obesity drive breast cancer risk and progression. Here, we determined that ETV4 directly associates with a poor prognosis for patients with ER-positive tumors and positively correlates with FGF1 levels in the context of obesity. We demonstrate that ETV4 is required to mediate the pro-tumorigenic effects of FGF1 on cell proliferation, glycolytic reprogramming, and tamoxifen sensitivity in vitro, and on tumor growth in the presence of estrogen in obese mice. In vitro, ETV4 overexpression enhances proliferation and metabolic activity, mimicking effects of FGF1 on breast cancer cells, but it is not sufficient to promote ER-positive tumor growth before or after estrogen deprivation in vivo in lean females. This study reveals a potentially novel mechanism through which weight gain, characterized by excess FGF1 production, drives the development of aggressive features in the prevalent ER-positive breast cancer subtype.

cancer biology↗

bioRxiv2025

Mouse scalp development requires Rac1 and SRF for the maintenance of mechanosensing mesenchyme

Regulation of essential cellular responses like proliferation, migration, and differentiation is crucial for normal development. Rac1, a ubiquitously expressed small GTPase, executes these responses under the regulation of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GTPases). Mutations in specific GEFs (DOCK6) and GTPases (AHGAP31) that regulate Rac1 are associated with Adams-Oliver syndrome (AOS), a developmental syndrome characterized by congenital scalp defects and limb truncations. Genetic ablation of Rac1 in the mouse embryonic limb ectoderm results in limb truncation. However, the etiology of Rac1-associated cranial defects is unknown. To investigate the origin and nature of cranial defects, we used a mesenchymal Cre line (Pdgfra-Cre) to delete Rac1 in cranial mesenchyme. Rac1-KO mice died perinatally and lacked the apical portion of the calvarium and overlying dermis, resembling cranial defects seen in severe cases of AOS. In control embryos, -smooth muscle actin (SMA) expression was spatially restricted to the apical mesenchyme, suggesting a mechanical interaction between the growing brain and the overlying mesenchyme. In Rac1-KO embryos there was reduced proliferation of apical mesenchyme, and reduced expression of SMA and its regulator, serum response factor (SRF). Remarkably, Srf-KO mice generated with Pdgfra-Cre recapitulated the cranial phenotype observed in Rac1-KO mice. Together, these data suggest a model where Rac1 and SRF are critical to maintaining apical fibroblasts in a mechano-sensitive and proliferative state needed to complete cranial development.

developmental biology↗