RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer

Lee, S.E.; Lee, J.U.; Lee, Hyo-Geun; Ryu, Min Jeong; Kim, S.J.; Kim, Y.K.; Choi, Min Jeong; Kim, K.S.; Kim, J.M.; Kim, J.W.; Koh, Yoon Woo; Lim, Dae–Sik; Jo, Young Suk; Shong, Minho

doi:10.1038/oncsis.2013.12

Cited by 27 publications

(21 citation statements)

References 59 publications

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“…30 Likewise, similar experimental data obtained in a prior study published by Liu et al 27 revealed that the expression levels of autophagy markers, including Beclin-1, LC3I 30 Likewise, similar experimental data obtained in a prior study published by Liu et al 27 revealed that the expression levels of autophagy markers, including Beclin-1, LC3I…”

Section: Silencing Of Tnrc6c-as1 Inhibited Tumorigenesis In Nude Micesupporting

confidence: 64%

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Yang

Guo

et al. 2019

Cell Proliferation

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Objectives: Thyroid carcinoma (TC) represents a malignant neoplasm affecting the thyroid. Current treatment strategies include the removal of part of the thyroid; however, this approach is associated with a significant risk of developing hypothyroidism.In order to adequately understand the expression profiles of TNRC6C-AS1 and STK4and their potential functions in TC, an investigation into their involvement with Hippo signalling pathway and the mechanism by which they influence TC apoptosis and autophagy were conducted.Methods: A microarray analysis was performed to screen differentially expressed lncRNAs associated with TC. TC cells were employed to evaluate the role of TNRC6C-AS1 by over-expression or silencing means. The interaction of TNRC6C-AS1 with methylation of STK4 promoter was evaluated to elucidate its ability to elicit autophagy, proliferation and apoptosis.Results: TNRC6C-AS1 was up-regulated while STK4 was down-regulated, where methylation level was elevated. STK4 was verified as a target gene of TNRC6C-AS1, which was enriched by methyltransferase. Methyltransferase's binding to STK4 increased expression of its promoter. Over-expressed TNRC6C-AS1 inhibited STK4 by promoting STK4 methylation and reducing the total protein levels of MST1 and LATS1/2. The phosphorylation of YAP1 phosphorylation was decreased, which resulted in the promotion of SW579 cell proliferation and tumorigenicity.Conclusion: Based on our observations, we subsequently confirmed the anti-proliferative, pro-apoptotic and pro-autophagy capabilities of TNRC6C-AS1 through STK4 methylation via the Hippo signalling pathway in TC.

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Section: Silencing Of Tnrc6c-as1 Inhibited Tumorigenesis In Nude Micesupporting

confidence: 64%

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Yang

Guo

et al. 2019

Cell Proliferation

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“…Ligand-specific receptor tyrosine kinase activation is a druggable target in RAI-refractory thyroid cancers (36)(37)(38). Recently, MEK-ERK independent signaling pathways involved in thyroid carcinogenesis have been investigated (39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Sirt1 induction confers resistance to etoposide-induced genotoxic apoptosis in thyroid cancers

Kweon

Lee

Jung

et al. 2014

International Journal of Oncology

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Despite the favorable therapeutic outcomes reported in differentiated thyroid cancer (DTC), a significant proportion of DTC patients present with refractory behavior to conventional therapy. The sirtuin (Sirt) family has recently been implicated in the maintenance of cellular homeostasis under genotoxic stress. Here, we investigated the induction of Sirt1 expression by etoposide-induced genotoxic stress to gain insights into thyroid carcinogenesis and identify novel therapeutic targets. Immunohistochemical staining analyses of Sirt1 and Sirt3 were performed using human thyroid cancer tissues and matched normal tissues, and bioinformatic analyses were done using public repositories, including the Human Protein Atlas, BioGPS, NCBI Gene Expression Omnibus (GEO) profiles, and GeneNetwork. TPC1, FTC133 and FRO cells were used for molecular biological experiments including apoptosis assays, MTT, immunofluorescence staining and qRT-PCR assays. The IHC data and public repositories data consistently showed variable Sirt1 and Sirt3 expression patterns in normal thyroid follicular cells and papillary thyroid cancer cells. The induction of Sirt1 and Sirt3 was cell type-specific and the expression levels of these genes correlated with apoptotic cell death and cell viability after etoposide-induced genotoxic stress. Sirt1‑Foxp3 signaling-mediated regulation of Bax and p21 mRNA expression was a signature molecular event in TPC1 cells, which showed remarkable resistance to etoposide-induced genotoxic stress. The induction of Sirt1 and Sirt3 may be a determinant of thyroid cancer cell survival under genotoxic stress conditions. Further examination of the Sirt1-Foxp3 signal may improve our understanding of thyroid carcinogenesis and help identify new druggable targets.

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“…The cascade of MST1/2 and LATS1/2 signalling was demonstrated to inactivate YAP1 by promoting its inhibitory Ser127 (S127) site phosphorylation, cytoplasmic retention and proteasome-mediated degradation 34 . Activation of YAP1 due to the gene amplification or the loss-of-function of MST1/2 or LATS1/2 is linked to the aetiology of many cancers including lung 35 , colon 36 , ovarian 37 , head and neck 38 , liver 39,40 , meningioma 41 , thyroid 42 and stomach 43 . In addition, emerging evidence suggests that YAP1 may also play a critical role in the pathobiology of PC 44 .…”

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confidence: 99%

YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer

Abali

Alptekin

Lewis³

et al. 2015

Nat Commun

100

142

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The transcriptional co-activator Yes-associated protein 1 (YAP1), a key nuclear effector of the Hippo pathway, is a potent oncogene, and yet, the interaction between YAP1 and androgen receptor (AR) remains unexplored. Here we identify YAP1 as a physiological binding partner and positive regulator of AR in prostate cancer. YAP1 and AR co-localize and interact with each other predominantly within cell nuclei by an androgen-dependent mechanism in a hormone naive and an androgen-independent mechanism in castration-resistant prostate cancer cells. The growth suppressor MST1 kinase modulates androgen-dependent and -independent nuclear YAP1–AR interactions through directly regulating YAP1 nuclear accumulation. Disruption of YAP1 signalling by genetic (RNAi) and pharmacological (Verteporfin) approaches suppresses AR-dependent gene expression and prostate cancer cell growth. These findings indicate that the YAP1–AR axis may have a critical role in prostate cancer progression and serves as a viable drug target.

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RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer

Cited by 27 publications

References 59 publications

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Sirt1 induction confers resistance to etoposide-induced genotoxic apoptosis in thyroid cancers

YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer

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