The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises

Ortega, Ángel; Vera, Ivana; Díaz, María P.; Navarro, Carla; Rojas, Milagros; Torres, Wheeler; Parra, Heliana; Salazar, Juan; Sanctis, Juan B. De; Bermúdez, Valmore

doi:10.3390/ijms23010430

Cited by 32 publications

(37 citation statements)

References 161 publications

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“…YAP/TAZ-mediated resistance induction is achieved by coupling these cofactors to transcriptional enhanced associate domain (TEAD) and its potentiators, increasing the transcriptional activity of the genome that determines cellular function and response. This event leads to a reduction in the effectiveness of anticancer treatments by reducing the sensitivity of cancer cells to these treatments [ 38 ]. Thus, FSCN1 may be a drug target for the treatment of prostate cancer, which can inhibit the development of prostate cancer by inhibiting FSCN1.…”

Section: Discussionmentioning

confidence: 99%

FSCN1 Promotes Glycolysis and Epithelial-Mesenchymal Transition in Prostate Cancer through a YAP/TAZ Signaling Pathway

Gao

Ding

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. The aim of the study is to investigate the role and possible mechanism of fascin-1 (FSCN1) in the invasion, migration, glycolysis, and epithelial-mesenchymal transition (EMT) of prostate cancer. Methods. Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to determine the mRNA expression level of FSCN1 in prostate cancer tissues and prostate cancer cells PC-3 and DU145. The transwell and the scratch test were applied to detect the invasion and migration abilities of cells, respectively. A metabolic assay was used for measuring the glucose consumption, lactate production, and the extracellular acidification rate (ECAR) in cells; western blot was used for checking FSCN1, EMT, and yes-associated protein/transcriptional co-activators with the PDZ-binding motif (YAP/TAZ) signaling pathway-related protein expression level in cells or tissues. Results. FSCN1 was significantly highly expressed in prostate cancer tissues and cells. On the one hand, interference with the expression of FSCN1 could inhibit the invasion, migration, EMT, and glycolysis of prostate cancer cells. On the other hand, overexpression of FSCN1 promoted the invasion, migration, EMT, and glycolysis of prostate cancer cells. Besides, further mechanistic studies revealed that FSCN1 could activate the YAP/TAZ signaling pathway in prostate cancer cells. Conclusion. FSCN1 promotes invasion, migration, EMT, and glycolysis in prostate cancer cells by activating the YAP/TAZ signaling pathway. FSCN1 may be used as a biomarker for the diagnosis or treatment in prostate cancer.

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Section: Discussionmentioning

confidence: 99%

FSCN1 Promotes Glycolysis and Epithelial-Mesenchymal Transition in Prostate Cancer through a YAP/TAZ Signaling Pathway

Gao

Ding

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Ren Y ( 84 ) proposed that CXCR3 induced metabolic alteration in SOR-resistance hepatocellular carcinoma cells through downregulating AMPK pathway activity and lipid peroxidation as well as upregulating levels of adipocytokines. In addition, some components (such as YAP/TAZ molecules and hypoxia-inducible factor-1) in the tumor microenvironment involved in mediating the altered metabolic pathways appear to be critical therapeutic targets that can be used to enhance current cancer treatment for metastatic and treatment-resistant cancers ( 85 , 86 ).…”

Section: Resultsmentioning

confidence: 99%

“…As we can see from the overall change tendency of burst keywords, the research hotspot has experienced a transition to precision cancer medicine. Besides, it’s interesting to note that three burst keywords including “tumor microenvironment” (2020–2022) ( 85 ), “invasion” (2019-2022) ( 108 ), and “target” (2019–2022) ( 109 ) are still ongoing. Metabolic signatures within the tumor microenvironment impact the immune function, therefore, overcoming individualized microenvironment-related resistance and identifying related novel targets and signatures will be research hotspots in the future ( 110 ).…”

Section: Resultsmentioning

confidence: 99%

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis

et al. 2022

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BackgroundCancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. Since Warburg O first observed alterations in cancer metabolism in the 1950s, people gradually found tumor metabolism pathways play a fundamental role in regulating the response to chemotherapeutic drugs, and the attempts of targeting tumor energetics have shown promising preclinical outcomes in recent years. This study aimed to summarize the knowledge structure and identify emerging trends and potential hotspots in metabolic signaling pathways of tumor drug resistance research.MethodsPublications related to metabolic signaling pathways of tumor drug resistance published from 1992 to 2022 were retrieved from the Web of Science Core Collection database. The document type was set to articles or reviews with language restriction to English. Two different scientometric software including Citespace and VOS viewer were used to conduct this scientometric analysis.ResultsA total of 2,537 publications including 1,704 articles and 833 reviews were retrieved in the final analysis. The USA made the most contributions to this field. The leading institution was the University of Texas MD Anderson Cancer Center. Avan A was the most productive author, and Hanahan D was the key researcher with the most co-citations, but there is no leader in this field yet. Cancers was the most influential academic journal, and Oncology was the most popular research field. Based on keywords occurrence analysis, these selected keywords could be roughly divided into five main topics: cluster 1 (study of cancer cell apoptosis pathway); cluster 2 (study of resistance mechanisms of different cancer types); cluster 3 (study of cancer stem cells); cluster 4 (study of tumor oxidative stress and inflammation signaling pathways); and cluster 5 (study of autophagy). The keywords burst detection identified several keywords as new research hotspots, including “tumor microenvironment,” “invasion,” and “target”.ConclusionTumor metabolic reprogramming of drug resistance research is advancing rapidly. This study serves as a starting point, providing a thorough overview, the development landscape, and future opportunities in this field.

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“…Interestingly, both proteins have been demonstrated to be directly involved in the EMT (28) (51), a process crucial in carcinoma metastasization. The forced expression of YAP in cancer cells is su cient to induce EMT, thus fostering tumor progression (52,53).…”

Section: Discussionmentioning

confidence: 99%

Extracellular signal-Regulated Kinase 5 (ERK5) is required for the Yes-associated protein (YAP) co-transcriptional activity

Marchetti

Ippolito

Consalvi

et al. 2022

Preprint

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YES-associated protein (YAP) is a transcriptional cofactor with a key role in the regulation of several cellular processes, including proliferation, differentiation and epithelial-to-mesenchymal transition (EMT), by integrating multiple cell autonomous and microenvironmental cues. YAP overexpression was found in different types of human cancer where it is associated with the acquisition of stemness properties, chemoresistance, increased cell proliferation and survival, metastasis and, ultimately, poor prognosis. YAP is the main downstream effector of the Hippo pathway, a tumor suppressive signaling able to transduce several extracellular signals. The Hippo pathway acts restraining YAP activity, since its activation induces YAP phosphorylation and cytoplasmic sequestration. However, recent observations indicate that YAP activity can be also modulated by Hippo independent/integrating pathways, still largely unexplored. In this study, we demonstrated the role of the extracellular signal-regulated kinase 5 (ERK5)/mitogen-activated protein kinase in the regulation of YAP activity. By means of ERK5 inhibition/silencing and overexpression experiments, and by using as model liver stem cells, hepatocytes and hepatocellular carcinoma (HCC) cell lines, we provided evidence that ERK5 is required for YAP-dependent gene expression. Mechanistically, ERK5 controls the recruitment of YAP on promoters of target genes and its physical interaction with the transcriptional partner TEAD; moreover, it mediates the YAP activation occurring in cell adhesion, migration and TGFβ-induced EMT of liver cells. Furthermore, we demonstrated that ERK5 signaling modulates YAP activity in a LATS1/2-independent manner. Therefore, our observations identify ERK5 as a novel upstream Hippo-independent regulator of YAP activity, thus unveiling a new target for therapeutic approaches aimed at interfering with its function.

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The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises

Cited by 32 publications

References 161 publications

FSCN1 Promotes Glycolysis and Epithelial-Mesenchymal Transition in Prostate Cancer through a YAP/TAZ Signaling Pathway

FSCN1 Promotes Glycolysis and Epithelial-Mesenchymal Transition in Prostate Cancer through a YAP/TAZ Signaling Pathway

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis

Extracellular signal-Regulated Kinase 5 (ERK5) is required for the Yes-associated protein (YAP) co-transcriptional activity

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