TEAD4 overexpression suppresses thyroid cancer progression and metastasis in vitro by modulating Wnt signaling

Zhang, Buyong; Wang, Qingqing; Ji, Yanting; Zhang, Xuan; Xue, Lingbo; Shi, Qingfeng; Li, Jie

doi:10.1007/s12038-021-00238-3

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…By contrast, Zhang et al showed that TEAD4 seems to play a tumor suppressor role in thyroid cancer. Overexpressed TEAD4 suppresses thyroid cancer progression and metastasis via maintaining an appropriate Wnt signaling by upregulating Wnt3a ( Zhang et al, 2022 ). The role of each TEAD member and its interaction with YAP or other co-factors would be necessary to clarify the role of TEADs in thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

TEAD4 as an Oncogene and a Mitochondrial Modulator

Hsu

Lin

et al. 2022

Front. Cell Dev. Biol.

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TEAD4 (TEA Domain Transcription Factor 4) is well recognized as the DNA-anchor protein of YAP transcription complex, which is modulated by Hippo, a highly conserved pathway in Metazoa that controls organ size through regulating cell proliferation and apoptosis. To acquire full transcriptional activity, TEAD4 requires co-activator, YAP (Yes-associated protein) or its homolog TAZ (transcriptional coactivator with PDZ-binding motif) the signaling hub that relays the extracellular stimuli to the transcription of target genes. Growing evidence suggests that TEAD4 also exerts its function in a YAP-independent manner through other signal pathways. Although TEAD4 plays an essential role in determining that differentiation fate of the blastocyst, it also promotes tumorigenesis by enhancing metastasis, cancer stemness, and drug resistance. Upregulation of TEAD4 has been reported in several cancers, including colon cancer, gastric cancer, breast cancer, and prostate cancer and serves as a valuable prognostic marker. Recent studies show that TEAD4, but not other members of the TEAD family, engages in regulating mitochondrial dynamics and cell metabolism by modulating the expression of mitochondrial- and nuclear-encoded electron transport chain genes. TEAD4’s functions including oncogenic activities are tightly controlled by its subcellular localization. As a predominantly nuclear protein, its cytoplasmic translocation is triggered by several signals, such as osmotic stress, cell confluency, and arginine availability. Intriguingly, TEAD4 is also localized in mitochondria, although the translocation mechanism remains unclear. In this report, we describe the current understanding of TEAD4 as an oncogene, epigenetic regulator and mitochondrial modulator. The contributing mechanisms will be discussed.

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Section: Introductionmentioning

confidence: 99%

TEAD4 as an Oncogene and a Mitochondrial Modulator

Hsu

Lin

et al. 2022

Front. Cell Dev. Biol.

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“…As one main component of the Hippo pathway, TEAD4 is a transcriptional enhancer–associated domain (TEAD) family protein ( Pobbati and Hong, 2013 ) that plays biological roles by binding with DNA elements via its specific DNA-binding domains or through interaction with transcription coactivators (i.e., YAP/TAZ) by transactivation domains ( Zhou et al, 2017 ; Gu et al, 2020 ). More recently, TEAD4 has been demonstrated in tumorigenesis and cancer progression, including cancers of the breast ( He et al, 2019 ; Wu Y et al, 2021 ), prostate ( Chen CL et al, 2021 ), gastric ( Shuai et al, 2020 ), bladder ( Wu et al, 2019 ; Wang J et al, 2021 ), thyroid ( Zhang et al, 2022 ), and lungs ( Zhou et al, 2017 ; Gu et al, 2020 ; Hu et al, 2021 ; Yan et al, 2022 ). Previous studies have reported that TEAD4 is upregulated in LUAD and is closely related to disease prognosis ( Hu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A Four-Gene Prognostic Signature Based on the TEAD4 Differential Expression Predicts Overall Survival and Immune Microenvironment Estimation in Lung Adenocarcinoma

Gong

Sun

et al. 2022

Front. Pharmacol.

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Background: TEA domain transcription factor 4 (TEAD4) is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which is studied to be linked to the tumorigenesis and progression of various forms of cancers, including lung adenocarcinoma (LUAD). However, the specific function of this gene in the progression of LUAD remains to be explored.Method: A total of 19 genes related to the Hippo pathway were analyzed to identify the significant genes involved in LUAD progression. The TCGA-LUAD data (n = 585) from public databases were mined, and the differentially expressed genes (DEGs) in patients with the differential level of TEAD4 were identified. The univariate Cox regression, zero LASSO regression coefficients, and multivariate Cox regression were performed to identify the independent prognostic signatures. The immune microenvironment estimation in the two subgroups, including immune cell infiltration, HLA family genes, and immune checkpoint genes, was assessed. The Gene Set Enrichment Analysis (GSEA) and GO were conducted to analyze the functional enrichment of DEGs between the two risk groups. The potential drugs for the high-risk subtypes were forecasted via the mode of action (moa) module of the connectivity map (CMap) database.Results:TEAD4 was found to be significantly correlated with poor prognosis in LUAD-patients. A total of 102 DEGs in TEAD4-high vs. TEAD4-low groups were identified. Among these DEGs, four genes (CPS1, ANLN, RHOV, and KRT6A) were identified as the independent prognostic signature to conduct the Cox risk model. The immune microenvironment estimation indicated a strong relationship between the high TEAD4 expression and immunotherapeutic resistance. The GSEA and GO showed that pathways, including cell cycle regulation, were enriched in the high-risk group, while immune response-related and metabolism biological processes were enriched in the low-risk group. Several small molecular perturbagens targeting CFTR or PLA2G1B, by the mode of action (moa) modules of the glucocorticoid receptor agonist, cyclooxygenase inhibitor, and NFkB pathway inhibitor, were predicted to be suited for the high-risk subtypes based on the high TEAD4 expression.Conclusion: The current study revealed TEAD4 is an immune regulation–related predictor of prognosis and a novel therapeutic target for LUAD.

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