ArticleCellular and molecular life sciences : CMLS2020
Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 98 citations in OpenAlex.
- Ketogenic Diet as an Adjuvant in Epithelial Cancers: Mechanisms, Model Systems, and Translational Opportunities.Cancers · 2026Review
- Targeting metabolic reprogramming in HPV-associated oral squamous cell carcinoma: current advances, challenges, and clinical prospects.Journal of molecular histology · 2026Review
- Cancer-associated fibroblasts as a target in head and neck squamous cell carcinoma: bridging mechanisms to therapy with drugs, adjuvants, and nanotechnology.Discover oncology · 2026Review
- Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review).International journal of molecular medicine · 2026Review
- Natural product-induced apoptosis in oral squamous cell carcinoma via targeting mitochondrial multifunctionality.Frontiers in oncology · 2026Review
- Mitochondrial-targeted therapeutics in oral squamous cell carcinoma: molecular and therapeutic implications.Frontiers in medicine · 2026Review
- Mitophagy-driven immune evasion in skin cancer: multidimensional regulatory networks and context-dependent therapeutic strategies-a narrative review.Frontiers in immunology · 2026Review
- Article
- lncRNA ADAMTS9-AS2/let-7a-5p axis regulates metabolic reprogramming by targeting HK2 in oral submucous fibrosis-associated oral squamous cell carcinoma.Genes & diseases · 2025Article
- PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP.eLife · 2025Article
- Article
- Nanotherapies Based on ROS Regulation in Oral Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts.Frontiers in molecular biosciences · 2025Article
- Advances in targeting cancer-associated fibroblasts through single-cell spatial transcriptomic sequencing.Biomarker research · 2024Review
- Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.Journal of translational medicine · 2024Article
- PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy.Cancer cell international · 2024Article
- The NADInternational journal of biological sciences · 2024Article
- Extracellular vesicles from cancer cell lines of different origins drive the phenotype of normal oral fibroblasts in a CAF-like direction.Frontiers in oncology · 2024Article
- Heterogeneity of cancer-associated fibroblasts and tumor-promoting roles in head and neck squamous cell carcinoma.Frontiers in molecular biosciences · 2024Review
- The hidden messengers: cancer associated fibroblasts-derived exosomal miRNAs as key regulators of cancer malignancy.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Cancers show a metabolic shift towards aerobic glycolysis. By "corrupting" their microenvironment, carcinoma cells are able to obtain energy substrates to "fuel" their mitochondrial metabolism and cell growth in an autophagy-associated, paracrine manner. However, the metabolic changes and role of normal fibroblasts in this process remain unclear. We devised a novel, indirect co-culture system to elucidate the mechanisms of metabolic coupling between stromal cells and oral squamous cell carcinoma (OSCC) cells. Here, we showed that normal oral fibroblasts (NOFs) and OSCC become metabolically coupled through several processes before acquiring an activated phenotype and without inducing senescence. We observed, for the first time, that NOFs export mitochondria towards OSCCs through both direct contact and via indirect mechanisms. NOFs are activated and are able to acquire a cancer-associated fibroblasts metabolic phenotype when co-cultivation with OSSC cells, by undergoing aerobic glycolysis, secreting more reactive oxygen species (ROS), high L-lactate and overexpressing lactate exporter MCT-4, leading to mitochondrial permeability transition pore (mPTP) opening, hypoxia, and mitophagy. On the other hand, Cav-1-low NOFs generate L-lactate to "fuel" mitochondrial metabolism and anabolic growth of OSCC. Most interestingly, the decrease in AMPK activity and PGC-1α expression might involve in regulation of ROS that functions to maintain final energy and metabolic homeostasis. This indicated, for the first time, the existence of ATP and ROS homeostasis during carcinogenesis. Our study suggests that an efficient therapeutical approach has to target the multiple mechanisms used by them to corrupt the normal surrounding stroma and metabolic homeostasis.
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