Late occurrence of breast cancer brain metastases in patients pretreated with systemic therapies is often associated with therapy resistant brain metastatic lesions. Prior studies targeting previously identified mediators of resistance have yielded limited success, especially in the case of brain metastatic breast cancer (BMBC). Trefoil Factor 1 (TFF1) has been associated with therapy resistance in estrogen receptor (ER) positive breast cancer. However, its role in therapy resistance of triple negative and HER2+ breast cancer remains elusive. Herein, we assessed the involvement of TFF1 in therapy resistant triple negative and HER2+ BMBC. We developed Paclitaxel resistant triple negative and Lapatinib resistant HER2+ BMBC cells by dose escalation method. Drug efflux transporter ABCB1 in Paclitaxel resistant cells and ABCG2 in Lapatinib resistant cells were significantly upregulated. Additionally, cancer stem cell marker, CD24, showed significant upregulation in both resistant cell lines while anti-apoptotic protein BCL2 was upregulated only in Lapatinib resistant cells. Importantly, TFF1 was significantly upregulated in both Paclitaxel and Lapatinib resistant BMBC cells. Moreover, siRNA mediated TFF1 silencing partially alleviated resistance in both Paclitaxel and Lapatinib resistant BMBC cells. Our study shows that TFF1 is potentially associated with resistance to Paclitaxel and Lapatinib in both triple negative and HER2+ BMBC.
Plant cells are turgid and exert pressure against a stiff extracellular matrix (ECM), the plant cell wall, which resists turgor pressure and prevents cell bursting due to osmotic pressure. During growth, the cell wall yields under turgor pressure and deforms to guide the expansion of the cytoplasm. Together, these suggest that the mechanical properties of the cell wall are tightly regulated during development and that a tight coordination between turgor pressure and cell wall plasticity is required. In this review, we explore the anisotropic mechanical properties of the cell wall and the mechanisms involved in its regulation. We discuss some of the theories supporting passive regulation of the cell wall such as the multinet theory and the scaffolding theory. We then discuss the role of CrRLK1Ls such as FERONIA and mechanosensing ion channels like MSL8 in the perception of mechanical stress and the role of Ca 2+ as a central secondary messenger of mechanical stress response. Finally, we highlight some of the transcriptional responses induced by mechanosensing via small signal peptides such as SCOOP and Pep1 and cell wall remodelling enzymes such as TCH4.
The 3rd Codon Usage Conference: Function, Mechanism and Evolution was held from 31 May to 3 June 2026, at the Bibliothèque et Archives nationales du Québec in Montreal, Canada. Here, I provide summaries of the talks that were given at the meeting, and I discuss major advancements in the field.
Ceramide-1-phosphate (C1P), once considered a minor metabolic intermediate, is now recognized as a relevant regulator of cell survival, inflammation, migration, oxidative stress, glucose uptake, and adipogenesis. These diverse functions are mediated by direct interactions between C1P and specific protein targets, including enzymes, lipid transfer proteins, and signaling effectors (typically proteins). While C1P was demonstrated to regulate a variety of signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase kinase (MEK)/extracellularly regulated kinases (ERK) 1–2, or sphingomyelin synthase (SMS)/protein kinase-C-alpha (PKCα), this review namely focuses on the eight major proteins that directly interact with C1P: acidic sphingomyelinase (ASMase), serine palmitoyl transferase (SPT), Ca 2+ -dependent cytosolic phospholipase A 2 -alpha (cPLA 2 α), Gi protein-coupled receptors, C1P transfer protein (CPTP), sphingomyelinase phosphodiesterase like 3b (SMPDL3b), annexin A2-p11 (S100A10), and Kelch-like ECH-associated protein 1 (KEAP1). Understanding C1P-protein interactions provides a conceptual framework for targeting sphingolipid signaling in inflammation, cancer and metabolic diseases. Here, we summarize current evidence for C1P binding or functional modulation of these proteins, and highlight the implications of these interactions in inflammation, oxidative stress control, and disease pathogenesis.
