2026-10-14T21:16:47Z https://api.figshare.com/v2/oai

oai:figshare.com:article/29968666 2026-10-05T17:02:12Z category_24142 category_24166 category_24163 category_24148 item_type_3 month_year_10_2026

<b>A lactate-fatty acid loop drives prostate cancer bone colonization by mediating metabolic interplay between tumor cells and osteoblasts</b> Hai Wang (19958979) Cell metabolism Signal transduction Receptors and membrane biology Cellular interactions (incl. adhesion, matrix, cell wall) Bone metastasis Prostate cancer cancer metabolism <p dir="ltr">Bone metastases (BoM) develop in 60–90% of men with advanced prostate cancer (PCa) and are associated with a significantly decreased quality of life and 5-fold increased risk of mortality. However, current frontline treatments offer only marginal improvements in survival and symptom management. In this study, we investigated the metabolic landscape of BoM lesions of PCa and found that prostate tumors rewire their metabolism to adapt to the bone microenvironment, utilizing lactate as an alternative nutrient source. Beyond its previously reported role in oxidative phosphorylation (OXPHOS), lactate serves as a net carbon source for fatty acid synthesis (FAS) in bone-colonized cancer cells. In turn, these cancer cells produce oleic acid (OA), which enhances osteoblast activity and drives pathological osteogenesis. At the molecular level, we identified monocarboxylate transporter 1 (MCT1) as the key membrane transporter enabling prostate tumor cells to take up lactate from the bone microenvironment. This process is subtly regulated by the nuclear factor of activated T cells (NFAT) and extracellular glucose levels, which together control both the transcription of SLC16A1 and the stability of MCT1 protein in response to the unique environmental challenges in bone. Notably, genetic ablation of MCT1, as well as pharmacological inhibition using the MCT1 inhibitor AZD3965, significantly suppressed PCa growth in bone. These findings highlight MCT1 as a critical metabolic vulnerability in PCa BoM and suggest that targeting lactate uptake may offer a promising therapeutic strategy for this lethal disease.</p> 2026-10-05T17:02:12Z Dataset Dataset 10.6084/m9.figshare.29968666.v2 https://figshare.com/articles/dataset/_b_A_lactate-fatty_acid_loop_drives_prostate_cancer_bone_colonization_by_mediating_metabolic_interplay_between_tumor_cells_and_osteoblasts_b_/29968666 CC BY 4.0