2026/02/22 by Noemi Carosella, Chiara Pastorello, Jehan Waeytens +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Agricultural and Biological Sciences · #Mechanisms of cancer metastasis #Protein Kinase Regulation and GTPase Signaling #Aluminum toxicity and tolerance in plants and animals
paper · pdf · doi:10.1002/pro.70510
openalex publication_date 2026/02/22 · openalex created_date 2026/02/24 · openalex updated_date 2026/07/31
NDRG1 is a multifunctional regulatory human protein implicated in crucial cellular processes and acting as a central hub of a cancer-related interactome. In lung cancer, increased NDRG1 expression is associated with resistance to chemotherapy and is linked to the cellular response to nickel, a known tumor driver in air pollution. Although NDRG1 has been extensively studied in relation to cancer and lipid vesicle recycling, its precise molecular mechanisms remain poorly defined. To address this gap, the present work shifts the focus from previous cellular-level investigations into a molecular-level study of NDRG1, dissecting the effects of phosphorylation, metal binding, and lipid interactions. Specifically, we investigated the C-terminal intrinsically disordered region of the protein that is a key regulatory hub and an attractive target for drug development. Employing a multimodal approach, which combines circular dichroism (CD), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), Fourier-transform infrared spectroscopy (FT-IR), and isothermal titration calorimetry (ITC), we developed a mechanistic rationale for how phosphorylation modulates protein subcellular localization, lipid trafficking and storage, acting as a molecular switch that toggles NDRG1 between membrane-bound, adhesion-supporting states and soluble, signaling-competent conformations with metal-binding activity. These insights open potential opportunities for therapeutic intervention in nickel and pollution-driven lung cancer.