YAP: The nexus between metabolism and cardiac remodeling

Gao, Chen; Wang, Yibin

doi:10.1172/jci157664

Cited by 9 publications

(9 citation statements)

References 13 publications

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“…Accumulating evidence supported that high expression of GLUT1 was tightly associated with loss of thyroid tumor differentiation and greater biological invasiveness [5]. In addition, within the tumor cell membrane, GLUT1 was the main glucose transporter mediating 18 F-FDG transport. In our study, immunohistochemical staining data confirmed that the expression of GLUT1 was higher in PTC tissues than in paracarcinoma tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the hypoxic tumor microenvironment, dysregulation of certain signaling pathways also contributed to cancer metabolic rewiring. Recently, a connection between glucose metabolism and the Hippo pathway activity has been observed [11,12,18]. Hippo signaling pathway, as a highly conserved tumor suppressor pathway, mainly included mammalian Ste20-like kinases 1/2 (MST1/2) and large tumor suppressor 1/2 (LATS1/2), YAP and/or its paralog TAZ.…”

Section: Discussionmentioning

confidence: 99%

“…The RAIR-PTC, usually a sign of higher aggressiveness, less differentiated and worse prognosis, can be detected by [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/ CT) [2]. In particular, 18 F-FDG-PET/ CT is considered useful for the detection of recurrent or metastatic thyroid cancer in patients with negative radioiodine scans, especially those with a high thyroglobulin (Tg) level. There is an inverse relationship between iodine and FDG accumulation, the so-called ''flip-flop'' phenomenon, that is when differentiated thyroid cancer cells dedifferentiate they tend to lose their affinity for iodine with increased glucose demand [3].…”

Section: Introductionmentioning

confidence: 99%

“…There is an inverse relationship between iodine and FDG accumulation, the so-called ''flip-flop'' phenomenon, that is when differentiated thyroid cancer cells dedifferentiate they tend to lose their affinity for iodine with increased glucose demand [3]. Thus, it is commonly accepted that high 18 F-FDG uptake reflects poor differentiation in thyroid cancers. However, the molecular mechanisms underlying glucose/iodine metabolic reprograming in dedifferentiated thyroid cancer are not entirely comprehended.…”

Section: Introductionmentioning

confidence: 99%

“…Induction of RAS signaling by inactivation of Hippo results in aberrant activation of mitogen-activated protein kinase (MAPK) output, which is the most important pathway contributing to the occurrence, development and reduction of NIS in PTC [17]. Interestingly, the role of YAP is not limited to its oncogenic potential, but has also been shown to affect glucose metabolism by upregulation of genes involved in glycolysis and glucose transporters, such as GLUT1, which is also regulated by HIF-1α [11,18]. Furthermore, studies have found that YAP interacted with HIF-1α to directly activates the transcription of glucose metabolism genes and accelerate glycolysis in cancer cells [19][20].…”

Section: Introductionmentioning

confidence: 99%

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HIF-1α/YAP Signaling Rewrites Glucose/Iodine Metabolism Program to Promote Papillary Thyroid Cancer Progression

Song¹,

Qiu²,

Wang³

et al. 2023

Int. J. Biol. Sci.

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Background:The management of aggressive and progressive metastatic papillary thyroid cancer (PTC) is very difficult. An inverse relationship between radioiodine and F-18 fluorodeoxyglucose (FDG) uptake (''flip-flop'' phenomenon) is described for invasive PTC during dedifferentiation. However, no satisfactory biologic explanation for this phenomenon. Hypoxia is an important microenvironmental factor that promotes cancer progression and glycolysis. The Hippo-YAP is a highly conserved tumor suppressor pathway and contributes to cancer metabolic reprogramming. Thus, we investigated the underlying molecular mechanisms of glucose/iodine metabolic reprogramming in PTC, focusing on the tumor hypoxia microenvironment and Hippo-YAP signaling. Methods: Immunohistochemistry staining was conducted to evaluate the expressions of hypoxia-inducible factor 1α (HIF-1α), yes-associated protein (YAP), glucose transporters 1 (GLUT1) and sodium iodine symporter (NIS) in matched PTC and the adjacent noncancerous tissues. PTC cell lines were cultured under normoxic (20% O2) and hypoxic (1% O2) conditions and the glycolysis level and NIS expression were measured. Further, we characterized the molecular mechanism of glucose/iodine metabolic reprogramming in PTC cell. Finally, we validated the results in vivo by establishing subcutaneous xenografts in nude mice. Results:The expression levels of HIF1-α, YAP and GLUT1 were upregulated in PTC tissues and YAP expression was positively associated with HIF-1α, GLUT1 and TNM stages. Meanwhile, the expression of NIS was negatively correlated with YAP. Further, in vitro studies indicated that hypoxia-induced YAP activation was critical for accelerating glycolysis and reducing NIS expression in PTC cells. Inhibition of YAP had the opposite effects in vitro and tumorigenicity in vivo. Hypoxia inhibited the Hippo signaling pathway resulting in the inactivation of YAP phosphorylation, further promoting the nuclear localization of YAP in PTC cells. The mechanism is that hypoxic stress promoted YAP binding to HIF-1α in the nucleus and maintained HIF-1α protein stability. The YAP/HIF-1α complex bound and directly activated the GLUT1 transcription to accelerate glycolysis. Meanwhile, HIF-1α/YAP signaling might indirectly reduce the expression of NIS by promoting the output of MAPK signaling. In vivo studies confirmed the YAP-mediated reprogramming of glucose/iodine metabolism promoted PTC progression. Conclusions: Collectively, our data revealed a novel regulatory mechanism of the glucose/iodine metabolic program rewritten by HIF-1α/YAP signaling in PTC. Inhibition of HIF-1α/YAP signaling alone or in combination with other potential markers may effectively combat aggressive PTC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HIF-1α/YAP Signaling Rewrites Glucose/Iodine Metabolism Program to Promote Papillary Thyroid Cancer Progression

Song¹,

Qiu²,

Wang³

et al. 2023

Int. J. Biol. Sci.

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YAP/TAZ: Molecular pathway and disease therapy

Wei,

Hui,

Chen

et al. 2023

MedComm

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The Yes‐associated protein and its transcriptional coactivator with PDZ‐binding motif (YAP/TAZ) are two homologous transcriptional coactivators that lie at the center of a key regulatory network of Hippo, Wnt, GPCR, estrogen, mechanical, and metabolism signaling. YAP/TAZ influences the expressions of downstream genes and proteins as well as enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, and the transdifferentiation of fibroblasts into myofibroblasts. YAP/TAZ can also be regulated through epigenetic regulation and posttranslational modifications. Consequently, the regulatory function of these mechanisms implicates YAP/TAZ in the pathogenesis of metabolism‐related diseases, atherosclerosis, fibrosis, and the delicate equilibrium between cancer progression and organ regeneration. As such, there arises a pressing need for thorough investigation of YAP/TAZ in clinical settings. In this paper, we aim to elucidate the signaling pathways that regulate YAP/TAZ and explore the mechanisms of YAP/TAZ‐induce diseases and their potential therapeutic interventions. Furthermore, we summarize the current clinical studies investigating treatments targeting YAP/TAZ. We also address the limitations of existing research on YAP/TAZ and propose future directions for research. In conclusion, this review aims to provide fresh insights into the signaling mediated by YAP/TAZ and identify potential therapeutic targets to present innovative solutions to overcome the challenges associated with YAP/TAZ.

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