Epigenetic Reprogramming of Cancer-Associated Fibroblasts Deregulates Glucose Metabolism and Facilitates Progression of Breast Cancer

Becker, Lisa; O’Connell, Joyce T.; Vo, Annie P.; Cain, Margo P.; Tampe, Désirée; Bizarro, Lauren; Sugimoto, Hikaru; McGow, Anna K.; Asara, John M.; Lovisa, Sara; McAndrews, Kathleen M.; Zieliński, Rafał; Lorenzi, Philip L.; Zeisberg, Michael; Raza, Sughra; LeBleu, Valerie S.; Kalluri, Raghu

doi:10.1016/j.celrep.2020.107701

Cited by 196 publications

(144 citation statements)

References 70 publications

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“…It results in a decrease in lactate secretion and aerobic glycolysis. It was recently shown that extinction of PDK in αSMA+ fibroblasts co-injected with 4T1 cells in an orthotopic tumors model decreases tumor growth [ 77 ]. In the same study, the authors show that breast cancer derived human CAFs are pro-glycolytic compared to fibroblasts from benign lesions.…”

Section: Targeting Mitochondria To Counteract Caf-cancer Cells Symmentioning

confidence: 99%

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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Section: Targeting Mitochondria To Counteract Caf-cancer Cells Symmentioning

confidence: 99%

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

Nocquet

Juin

Souazé

2020

Cancers

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“…In prostate cancer, TGF-β derived from cancer cells activates fibroblasts via NADPH oxidase 4-mediated reactive oxygen species signaling [ 16 ]. Hypoxia causes the epigenetic reprogramming of breast fibroblasts, resulting in them gaining CAF-like pro-glycolytic phenotypes [ 17 ]. In addition, numerous miRNAs have been reported to be involved in the differentiation of normal fibroblasts into CAFs [ 18 ].…”

Section: Cancer-associated Fibroblasts (Cafs)mentioning

confidence: 99%

Long Non-Coding RNAs as Regulators of Interactions between Cancer-Associated Fibroblasts and Cancer Cells in the Tumor Microenvironment

Ahn

Kim²

2020

IJMS

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Long non-coding RNAs (lncRNAs) regulate diverse physiological and pathological processes via post-transcriptional, post-translational, and epigenetic mechanisms. They are also involved in tumor initiation, progression, and metastasis by functioning as key players in the tumor microenvironment. Cancer-associated fibroblasts (CAFs) promote tumor initiation, progression, metastasis, drug resistance, and immunosuppression, which can be modulated by lncRNAs. LncRNAs regulate the intrinsic properties of CAFs or cancer cells intracellularly or function extracellularly through exosomal secretion. In-depth studies on the mechanisms of lncRNA functions will enable their clinical use as diagnosis/prognosis markers and therapeutic targets in cancer treatment.

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“…CAFs, as other fibroblasts, possess spindle-shaped morphology (Figure 1), although gained increased proliferation rates [1]. CAFs are extensively described in literature, including [1,[7][8][9][10][12][13][14][15][16][17]. In particular, CAFs can be defined as a heterogenous population of connective tissue cells that contribute to cancer progression by secreting specific molecules, including growth factors, proteases, chemokines and cytokines.…”

Section: Cancer-associated Fibroblasts Tumor Microenvironment and Ramentioning

confidence: 99%

“…CAFs, which is the predominant cell type present in the tumor stroma, are involved in angiogenesis by secreting various pro-and antiangiogenic factors [74]. CAFs adapt to local hypoxia by changing metabolism and increasing, for example, glycolysis, catabolic activity, autophagy, as well as enhancing the VEGF signaling [1,17,[74][75][76]. For instance, CAFs were reported to deregulate glucose metabolism following epigenetic reprogramming and thus facilitating the progression of breast cancer [17].…”

Section: Hypoxia and Cafsmentioning

confidence: 99%

Interaction between Fibroblasts and Immune Cells Following DNA Damage Induced by Ionizing Radiation

Ragunathan

Upfold

Oksenych

2020

Preprint

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Cancer-associated fibroblasts (CAF) form the basis of tumor microenvironment and possess immunomodulatory functions by interacting with other cells surrounding tumor, including T lymphocytes, macrophages, dendritic cells and natural killer cells. Ionizing radiation is a broadly-used method in radiotherapy to target tumors. In mammalian cells, ionizing radiation induces various types of DNA damages and DNA damage response. Being unspecific, radiotherapy affects all the cells in tumor microenvironment, including the tumor itself, CAFs and immune cells. CAFs are extremely radio-resistant and do not initiate apoptosis even at high doses of radiation. However, following radiation, CAFs become senescent and produce a distinct combination of immunoregulatory molecules. Radiosensitivity of immune cells varies depending on the cell type due to inefficient DNA repair in, for example, monocytes and granulocytes. In this minireview, we are summarizing recent findings on the interaction between CAF, ionizing radiation and immune cells in the tumor microenvironment.

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Epigenetic Reprogramming of Cancer-Associated Fibroblasts Deregulates Glucose Metabolism and Facilitates Progression of Breast Cancer

Abstract: Highlights d Pro-glycolytic CAFs fuel cancer cell metabolism to support breast tumor growth d CAFs attain a pro-glycolytic phenotype by epigenetic control of glycolysis d Chronic hypoxia enables epigenetic reprogramming of glycolysis in fibroblasts

Cited by 196 publications

References 70 publications

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

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

Long Non-Coding RNAs as Regulators of Interactions between Cancer-Associated Fibroblasts and Cancer Cells in the Tumor Microenvironment

Interaction between Fibroblasts and Immune Cells Following DNA Damage Induced by Ionizing Radiation

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