ITGB4-mediated metabolic reprogramming of cancer-associated fibroblasts

Sung, Jin Sol; Kang, Chan Woo; Kang, Suki; Jang, Yeonsue; Chae, Young Chan; Kim, Baek Gil; Cho, Nam Hoon

doi:10.1038/s41388-019-1014-0

Cited by 118 publications

(98 citation statements)

References 37 publications

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“…51 Furthermore, the vital role of cancer cells-released exosomes in remodeling fibroblasts metabolism and promoting glycolysis were also confirmed in breast cancer cells. 52 , 53 Additionally, exosomes derived from cancer cells could induce the expression of MCT4 in CAFs to export β-HB and lactate into the cancer cells, and cancer cells expressing MCT1 utilize lactate to improve the level of OXPHOS. 53 , 54 All these results demonstrated that exosome-mediated metabolic reprogramming plays a crucial role in the intercellular communication between cancer cells and CAFs.…”

Section: Exosome-mediated Metabolic Reprogramming In the Tmementioning

confidence: 99%

Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

Yang

Wang

Gong

et al. 2020

Sig Transduct Target Ther

236

185

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Metabolic reprogramming is reported to be one of the hallmarks of cancer, which is an adaptive mechanism by which fast-growing cancer cells adapt to their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Meanwhile, the TME is a highly heterogeneous ecosystem incorporating cancer cells, fibroblasts, adipocytes, endothelial cells, mesenchymal stem cells, and extracellular matrix. Accumulated evidence indicates that exosomes may transfer biologically functional molecules to the recipient cells, which facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells and their surrounding stromal cells. In this review, we present the role of exosomes in the TME and the underlying mechanism of how exosomes exacerbate tumor development through metabolic reprogramming. In addition, we will also discuss the potential role of exosomes targeting metabolic process as biomarkers for tumor diagnosis and prognosis, and exosomes-mediated metabolic reprogramming as potential targets for cancer therapy. Furthermore, a better understanding of the link between exosomes and metabolic reprogramming, and their impact on cancer progression, would provide novel insights for cancer prevention and treatment in the future.

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Section: Exosome-mediated Metabolic Reprogramming In the Tmementioning

confidence: 99%

Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

Yang

Wang

Gong

et al. 2020

Sig Transduct Target Ther

236

185

View full text Add to dashboard Cite

show abstract

“…The knockdown of these proteins results in a decrease in EV release and the ability of EVs to promote recipient cell proliferation and migration [133,134]. Still, other EV proteins have been found to promote various CAF functions, including aerobic glycolysis (integrin subunit beta 4 (ITGB4)) and CAF recruitment to metastatic tumors (Lin-28 homolog B (LIN28B)), resistance to apoptosis (WW and C2 domain containing 2 (WWC2) and survivin), increased migration or proliferation (hyaluronidase-1 (Hyal1), sphingosine-1-phosphate receptor 2 (S1PR2)), and expression of MMPs (CD147) [123][124][125][126]128,129,131,132,135]. These results demonstrate the wide range of effects that cancer cell-derived EVs have on cells of the TME.…”

Section: Proteinsmentioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

Shoucair

Mello

Jabalee

et al. 2020

IJMS

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Extracellular vesicles (EVs) play a key role in the communication between cancer cells and stromal components of the tumor microenvironment (TME). In this context, cancer cell-derived EVs can regulate the activation of a CAF phenotype in TME cells, which can be mediated by several EV cargos (e.g., miRNA, proteins, mRNA and lncRNAs). On the other hand, CAF-derived EVs can mediate several processes during tumorigenesis, including tumor growth, invasion, metastasis, and therapy resistance. This review aimed to discuss the molecular aspects of EV-based cross-talk between CAFs and cancer cells during tumorigenesis, in addition to assessing the roles of EV cargo in therapy resistance and pre-metastatic niche formation.

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“…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 ]. A recent study has shown that triple negative breast cancer cells can induce CAF glycolytic switch and mitophagy via exosome-mediated integrin ITGB4 export that induces ITGB4 expression by CAFs themselves [ 55 ]. In these studies, cancer-cell-triggered glycolytic CAFs secrete lactate.…”

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%

“…Moreover, the secreted intermediates that modulate mitochondrial function are specific of certain subtypes of cancer. It seems the case with breast-cancer-cell-secreted ITGB4 that it is mainly secreted by triple negative breast cancer cell lines, and more specifically by some of the lines of this molecular subtype [ 55 ].…”

Section: Mitochondrial Processing In Cafs Is Implicated In Their Pmentioning

confidence: 99%

See 1 more Smart Citation

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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ITGB4-mediated metabolic reprogramming of cancer-associated fibroblasts

Cited by 118 publications

References 37 publications

Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

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

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