Biology subjects

Canovas, B.

Publications and source records attributed to Canovas, B..

3 recordsLinked to original sources

bioRxiv2026

Integrated molecular and functional profiling identifies E0771 as a basal-like triple-negative breast cancer model

Breast cancer is a heterogeneous disease whose clinical management relies heavily on accurate molecular subtyping. The murine E0771 mammary carcinoma cell line is widely used in preclinical studies, yet its molecular identity remains controversial, with reports variably classifying it as luminal B or triple-negative. In this study, we performed an integrated molecular and functional characterization of two independently sourced E0771 cell line stocks to resolve this discrepancy. Both stocks were genetically authenticated and exhibited concordant phenotypes. Immunohistochemical and molecular analyses demonstrated absence of oestrogen and progesterone receptors, classifying E0771 as triple-negative. Functionally, E0771 cells showed no transcriptional response to oestrogen and displayed resistance to endocrine therapy both in vitro and in vivo. Collectively, our results establish E0771 as an oestrogen-independent, basal-like triple-negative breast cancer model, supporting its appropriate use in studies of hormone-resistant breast cancer biology.

cancer biology↗

bioRxiv2024

The PIN1-p38-CtIP signaling axis protects stalled replication forks from deleterious degradation

Human CtIP plays a critical role in homologous recombination (HR) by promoting the resection of DNA double-strand breaks. Moreover, CtIP maintains genome stability through protecting stalled replication forks from nucleolytic degradation. However, the upstream signaling mechanisms governing the molecular switch between these two CtIP-dependent processes remain largely elusive. Here, we show that phosphorylation of CtIP by the p38 stress kinase and subsequent PIN1-mediated CtIP cis-to-trans isomerization is required for fork stabilization but dispensable for HR. We found that stalled forks are degraded in cells expressing non-phosphorylatable CtIP or lacking PIN1-p38 activity, while expression of a CtIP trans-locked mutant overcomes the requirement for PIN1-p38 in fork protection. We further reveal that Brca1-deficient mammary tumor cells that have acquired PARPi resistance regain chemosensitivity after PIN1 or p38 inhibition. Collectively, our findings identify the PIN1-p38-CtIP signaling pathway as a critical regulator of replication fork integrity.

molecular biology↗

bioRxiv2022

Characterization of p38a signaling networks in cancer cells using quantitative proteomics and phosphoproteomics

p38 (encoded by MAPK14) is a protein kinase that regulates cellular responses to almost all types of environmental and intracellular stresses. Upon activation, p38 phosphorylates many substrates both in the cytoplasm and nucleus, allowing this pathway to regulate a wide variety of cellular processes. While the role of p38 in the stress response has been widely investigated, its implication in cell homeostasis is less understood. To investigate the signaling networks regulated by p38 in normally proliferating cancer cells, we performed quantitative proteomic and phosphoproteomic analyses in breast cancer cells in which this pathway had been either genetically targeted or chemically inhibited. Our study identified with high confidence 35 proteins and 82 phosphoproteins (114 phosphosites) that are modulated by p38, and highlighted the implication of various protein kinases, including MK2 and mTOR, in the p38-regulated signaling networks. Moreover, functional analyses revealed an important contribution of p38 to the regulation of cell adhesion, DNA replication and RNA metabolism. Indeed, we provide experimental evidence supporting that p38 negatively regulates cell adhesion, and showed that this p38 function is likely mediated by the modulation of the adaptor protein ArgBP2. Collectively, our results illustrate the complexity of the p38 regulated signaling networks, provide valuable information on p38-dependent phosphorylation events in cancer cells, and document a mechanism by which p38 can regulate cell adhesion.

biochemistry↗