The role of YAP/TAZ activity in cancer metabolic reprogramming

Zhang, Xiaodong; Zhao, Haiying; Li, Yan; Xia, Di; Yang, Liang; Ma, Yingbo; Li, Hangyu

doi:10.1186/s12943-018-0882-1

Cited by 126 publications

(113 citation statements)

References 81 publications

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“…Many factors, particularly the tumor microenvironment and hypoxia, can regulate metabolic reprogramming to promote the malignant biological properties of tumors . Therefore, the differentially expressed genes (DEGs) in CCA were selected via TCGA database, and we confirmed that the most important DEGs were related to glucose homeostasis and gluconeogenesis by functional enrichment analysis (Figure A).…”

Section: Resultsmentioning

confidence: 99%

SIRT3 elicited an anti‐Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis

Yang

Zhou

et al. 2019

Cancer Medicine

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Cholangiocarcinoma (CCA) is an extremely invasive malignancy with late diagnosis and unfavorable prognosis. Surgery and chemotherapy are still not effective in improving outcomes in CCA patients. It is crucial to explore a novel therapeutic target for treating CCA. An NAD‐dependent deacetylase also known as Sirtuin‐3 (SIRT3) has been shown to regulate cellular metabolism in various cancers dynamically. However, the biological function of SIRT3 in CCA remains unclear. In this study, bioinformatics analyses were performed to identify the differentially expressed genes and pathways enriched. CCA samples were collected for immunohistochemical analysis. Three human CCA cell lines (HuCCT1, RBE, and HCCC9810) were used to explore the molecular mechanism of SIRT3 regulation of metabolic reprogramming and malignant behavior in CCA. A CCA xenograft model was then established for further validation in vivo. The data showed that SIRT3 expression was decreased and glycolysis was enhanced in CCA. Similar metabolic reprogramming was also observed in SIRT3 knockout mice. Furthermore, we demonstrated that SIRT3 could play an anti‐Warburg effect by inhibiting the hypoxia‐inducible factor‐1α (HIF1α)/pyruvate dehydrogenase kinase 1 (PDK1)/pyruvate dehydrogenase (PDHA1) pathway in CCA cells. CCA cell proliferation and apoptosis were regulated by SIRT3‐mediated metabolic reprogramming. These findings were further confirmed in CCA clinical samples and the xenograft model. Collectively, this study suggests that in the inhibition of CCA progression, SIRT3 acts through an anti‐Warburg effect on the downstream pathway HIF1α/PDK1/PDHA1.

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Section: Resultsmentioning

confidence: 99%

SIRT3 elicited an anti‐Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis

Yang

Zhou

et al. 2019

Cancer Medicine

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“…Moreover, recent studies showed that YAP contribute to cancer metabolic reprogramming [21,24], including glycolysis. As studies reported, the activation of YAP can promote glucose uptake and the rate of glycolysis in tumor cells [25][26][27]. However, few studies have reported on the relationship between the two roles of YAP.…”

Section: Introductionmentioning

confidence: 99%

Stiffer Matrix Accelerates Migration of Hepatocellular Carcinoma Cells through Enhanced Aerobic Glycolysis Via the MAPK-YAP Signaling

Liu

Luo

Deng

et al. 2020

Cancers

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Increased extracellular matrix (ECM) stiffness and metabolic reprogramming of cancer cells are two fundamental mediators of tumor progression, including hepatocellular carcinoma (HCC). Yet, the correlation between ECM stiffness and excessive aerobic glycolysis in promoting the development of HCC remains unknown. Here, we demonstrated that stiffer ECM promotes HCC cell migration depending on their accelerated aerobic glycolysis. Our results also indicated that stiffer ECM-induced YAP activation plays a major role in promoting aerobic glycolysis of HCC cells. Moreover, we showed that JNK and p38 MAPK signaling are critical for mediating YAP activation in HCC cells. Together, our findings established that the MAPK-YAP signaling cascade that act as a mechanotransduction pathway is essential for promoting HCC cell aerobic glycolysis and migration in response to ECM stiffness.

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“…Active endocytosis not only regulates PM SA in cells, but is also essential for controlling the surface distribution of a wide-range of membrane proteins including surface receptors and transporters (Antonescu et al, 2014;Bokel and Brand, 2014;Weinberg and Puthenveedu, 2018). Recent studies have suggested that surface expression of glucose transporters and the levels of cytoplasmic glucose can control YAP1 localization and activity (Santinon et al, 2015;Zhang et al, 2018). Therefore, one possibility is that increased CME upon cell fusion changes the distribution of glucose transporters leading to YAP1 nuclear exclusion.…”

Section: Increased Cme Upon Cell Fusion Results In Transient Glucose mentioning

confidence: 99%

Transcriptional reprogramming in fused cells is triggered by plasma-membrane diminution

Feliciano

Espinosa-Medina

Weigel

et al. 2019

Preprint

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Developing cells divide and differentiate, and in many tissues, such as bone, muscle, and placenta, cells fuse acquiring specialized functions. While it is known that fused-cells are differentiated, it is unclear what mechanisms trigger the programmatic-change, and whether cell-fusion alone drives differentiation. To address this, we employed a fusogen-mediated cell-fusion system involving undifferentiated cells in tissue culture. RNA-seq analysis revealed cell-fusion initiates a dramatic transcriptional change towards differentiation. Dissecting the mechanisms causing this reprogramming, we observed that after cell-fusion plasma-membrane surface area decreases through increased endocytosis. Consequently, glucose-transporters are internalized, and cytoplasmic-glucose and ATP transiently decrease. This low-energetic state activates AMPK, which inhibits YAP1, causing cell-cycle arrest. Impairing either endocytosis or AMPK prevents YAP1 inhibition and cell-cycle arrest after fusion. Together these data suggest that cell-fusion-induced differentiation does not need to rely on extrinsiccues; rather the plasma-membrane diminishment forced by the geometrictransformations of cell-fusion cause transient cell-starvation that induces differentiation. GLUCOSE [GLUC] AMPK [ATP] YAP1 NON-FUSED CELLS PROLIFERATIVE STATE Proliferation genes GLUCOSE [GLUC] [ATP] YAP1-P SYNCYTIUM DIFFERENTIATED STATE Differentiation genes GLUCOSE [GLUC] AMPK [ATP] LOW ENERGY STATE / REMODELING YAP1 CME Proliferation genes CELL FUSION Figure 8. Feliciano et al.

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The role of YAP/TAZ activity in cancer metabolic reprogramming

Cited by 126 publications

References 81 publications

SIRT3 elicited an anti‐Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis

SIRT3 elicited an anti‐Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis

Stiffer Matrix Accelerates Migration of Hepatocellular Carcinoma Cells through Enhanced Aerobic Glycolysis Via the MAPK-YAP Signaling

Transcriptional reprogramming in fused cells is triggered by plasma-membrane diminution

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