Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts

Zhang, Zhuoyuan; Gao, Zenghui; Rajthala, Saroj; Sapkota, Dipak; Dongre, Harsh; Parajuli, Himalaya; Suliman, Salwa; Das, Ridhima; Li, Longjiang; Bindoff, Laurence A.; Costea, Daniela Elena; Liang, Kristina Xiao

doi:10.1007/s00018-019-03209-y

Cited by 52 publications

(40 citation statements)

References 34 publications

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“…Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix and encodes 37 subunits of the tETC complex involved in the OxPhos system. Based on previous findings, HNSCC cells utilize aerobic glycolysis preferentially over the mitochondrial metabolism, suggesting that a decreased OxPhos activity is a potential predisposition for HNSCC development [21,81]. Indeed, it was found that a significantly lower mtDNA copy number was detected in the peripheral blood leukocytes of oral premalignant lesion patients when compared to those from a healthy group [82].…”

Section: Development Of Anti-cancer Scheme By Targeting Distinct Mmentioning

confidence: 99%

“…The first observation for determining the importance of CAFs in HNSCC was described by Rosenthal et al, showing that elevated TGF 1 was detected in the stromal counterpart of HNSCCs compared to normal mucosa [204]; the stroma-derived TGF 1 is important to the migration of Disseminated Tumor Cells (DTCs) [205]. Moreover, a co-culture of HNSCC/OSCC cells with CAFs could trigger an HNSCC cell proliferation, invasion and metastatic activity [206], as well as metabolic alteration [81]. The large-scale screening of secretome by CAFs was also carried out to more systemically identify stroma-specific molecules, and the results found that the epithelial-mesenchymal-transition (EMT) mediator S100 calcium-binding protein A4 (S100A4) serves as a potential therapeutic target for the CAFs-based treatment in HNSCCs [207].…”

Section: Molecular Basis Of Metabolic Regulations In Hnsccsmentioning

confidence: 99%

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Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

Hsieh¹,

Chen²,

Lin

et al. 2019

IJMS

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Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies. However, the following questions are still poorly understood: (i) how does metabolic reprogramming occur during HNSCC development? (ii) how does the tumorous milieu contribute to HNSCC tumourigenesis? and (iii) at the molecular level, how do various metabolic cues interact with each other to control the oncogenicity and therapeutic sensitivity of HNSCC? In this review article, the regulatory roles of different metabolic pathways in HNSCC and its microenvironment in controlling the malignancy are therefore discussed in the hope of providing a systemic overview regarding what we knew and how cancer metabolism could be translated for the development of anti-cancer therapeutic reagents.

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Section: Development Of Anti-cancer Scheme By Targeting Distinct Mmentioning

confidence: 99%

Section: Molecular Basis Of Metabolic Regulations In Hnsccsmentioning

confidence: 99%

Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

Hsieh¹,

Chen²,

Lin

et al. 2019

IJMS

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“…Indeed, prostate cancer cells induce glycolytic switch in CAFs via the downregulation of mitochondrial deacetylase SIRT3 that promotes oxidative stress and HIF1 stabilization [ 7 ]. Oral squamous cell carcinoma cells have also been shown to metabolically reprogram normal oral fibroblasts in an indirect co-culture model by inducing mitochondrial dysfunction reported as ROS accumulation, mitochondrial permeability transition pore opening, hypoxia and mitophagy, associated with an increase in aerobic glycolysis [ 53 ]. Moreover, breast cancer cells have been shown to favor CAF oxidative stress via hydrogen peroxide secretion, leading to CAF autophagy and mitophagy mediated by HIF1 stabilization, and promoting mitochondrial dysfunction and enhanced glycolysis [ 54 ].…”

Section: Mitochondrial Processing In Cafs Is Implicated In Their Pmentioning

confidence: 99%

“…In these studies, cancer-cell-triggered glycolytic CAFs secrete lactate. Importantly, this secretion is promoted by the upregulation of the monocarboxylate transporter MCT4 in CAFs [ 7 , 13 , 53 , 55 ].…”

Section: Mitochondrial Processing In Cafs Is Implicated In Their Pmentioning

confidence: 99%

“…Interestingly, the acquisition of CAFs’ metabolic characteristics by normal fibroblasts co-cultured with malignant cells precedes the acquisition of the fibroblast activation protein (FAP) and loss of Caveolin 1 [ 53 ]. This result suggests that metabolic reprogramming could participate in the activation of fibroblasts by cancer.…”

Section: Mitochondrial Processing In Cafs Is Implicated In Their Pmentioning

confidence: 99%

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Mitochondria at Center of Exchanges between Cancer Cells and Cancer-Associated Fibroblasts during Tumor Progression

Nocquet

Juin

Souazé

2020

Cancers

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Resistance of solid cancer cells to chemotherapies and targeted therapies is not only due to the mutational status of cancer cells but also to the concurring of stromal cells of the tumor ecosystem, such as immune cells, vasculature and cancer-associated fibroblasts (CAFs). The reciprocal education of cancer cells and CAFs favors tumor growth, survival and invasion. Mitochondrial function control, including the regulation of mitochondrial metabolism, oxidative stress and apoptotic stress are crucial for these different tumor progression steps. In this review, we focus on how CAFs participate in cancer progression by modulating cancer cells metabolic functions and mitochondrial apoptosis. We emphasize that mitochondria from CAFs influence their activation status and pro-tumoral effects. We thus advocate that understanding mitochondria-mediated tumor–stroma interactions provides the possibility to consider cancer therapies that improve current treatments by targeting these interactions or mitochondria directly in tumor and/or stromal cells.

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Cancer‐associated fibroblasts: Is it a key to an intricate lock of tumorigenesis?

Aden

Zaheer

Ahluwalia

et al. 2023

Cell Biology International

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The past few decades have witnessed a major leap in knowledge relating to the role of tumor microenvironment (TME) in carcinogenesis and evolving behavior of the tumor. Multiple factors within the TME modulate the cancer cells and the associated therapies. Stephen Paget first asserted that the microenvironment plays an important role in the growth of tumor metastasis. The most important player in the TME is cancer‐associated fibroblast (CAF) which significantly participates in the proliferation, invasion, and metastasis of tumor cells. CAFs show phenotypic and functional heterogeneity. Mostly CAFs originate from quiescent resident fibroblast or mesoderm‐derived precursor cells (mesenchymal stem cells), although several alternate sources of origin have been noted. However, due to lack of specific fibroblast‐restricted markers, it is very difficult to trace lineage and identify the biological origin of distinct subtypes of CAFs. CAFs are predominantly shown by several studies to mainly act as tumor‐promoting agents, however, tumor‐inhibiting actions are also being validated by several studies. A more objectified and comprehensive functional and phenotypic classification of CAF is required, which will help in better way for tumor management. Here, in this review, we have tried to review the current status of CAF origin, along with phenotypic and functional heterogeneity, and recent progress in CAF research.

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Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts

Cited by 52 publications

References 34 publications

Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

Mitochondria at Center of Exchanges between Cancer Cells and Cancer-Associated Fibroblasts during Tumor Progression

Cancer‐associated fibroblasts: Is it a key to an intricate lock of tumorigenesis?

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