Overexpression of Hippo pathway effector <scp>TAZ</scp> in tongue squamous cell carcinoma: correlation with clinicopathological features and patients' prognosis

Wei, Zhou; Wang, Yanling; Li, Zhongwu; Yuan, Chunping; Zhang, Wei; Wang, Dongmiao; Ye, Jinhai; Huang, Jiang; Wu, Yunong; Cheng, Jie

doi:10.1111/jop.12062

Cited by 37 publications

(44 citation statements)

References 32 publications

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“…34,35 The immunoreactivity in each slide was assessed independently by two senior oral pathologists without knowledge about the clinical and pathological information. Negative controls (without primary antibody incubation) were included in each staining run.…”

Section: Histopathological Evaluation and Immunohistochemistrymentioning

confidence: 99%

Oncogenic roles of Bmi1 and its therapeutic inhibition by histone deacetylase inhibitor in tongue cancer

Wang

Yuan

et al. 2014

Laboratory Investigation

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The polycomb complex protein Bmi1 (B lymphoma Mo-MLV insertion region 1 homolog) mediates epigenetic transcriptional silencing by modifying chromatin structure and is critical for stem cell homeostasis and tumorigenesis. Bmi1 is frequently overexpressed in human malignancies and therefore has key diagnostic and prognostic significance, and holds potential as a therapeutic target. Here we sought to characterize the expression patterns and oncogenic roles of Bmi1 in tongue squamous cell carcinoma and to determine the anticancer effects of histone deacetylase inhibitors (HDACis) via Bmi1 inhibition against tongue cancer. Our data revealed that Bmi1 was aberrantly overexpressed in a significant portion of tongue cancers. Elevated Bmi1 is associated with cervical node metastasis, Ki-67 abundance and reduced overall survival, and also serves as an independent prognostic factor for patient outcomes. Short-hairpin RNA-mediated Bmi1 knockdown inhibited cell proliferation and migration, induced cell apoptosis and senescence, reduced colony formation and CD44þ CD133 þ sub-population as well as enhanced cisplatin chemosensitivity, presumably by modulation of p16, p14 and E-cadherin. Moreover, HDACi chemicals Trichostatin A (TSA) and sodium butyrate (NaB) potently inhibited Bmi1 and triggered similar phenotypic changes reminiscent of Bmi1 silencing, although TSA treatment seemed paradoxically to induce some epithelial-mesenchymal transition-like changes in tongue cancer cells. Importantly, NaB-induced antitumor effects were partially attenuated by enforced Bmi1 overexpression in vitro. Genetic Bmi1 silencing and pharmacological inhibition of Bmi1 by NaB treatment significantly impaired tumor growth in a tongue cancer xenograft model. Taken together, our results indicate that Bmi1 serves as a key driver and biomarker with multiple oncogenic functions underlying tongue tumorigenesis. Selected appropriate HDACi compounds like NaB may represent novel therapeutic agents against tongue cancer. Oral cancer is one of the most common cancers worldwide, approximately accounting for 3% of all malignancies in both sexes. It is widely represented as a heterogeneous tumor with aggressive phenotypes and behaviors. The major etiological risks for this malignancy include smoking and alcohol consumption and human papillomavirus infection. 1 The overwhelming majority of oral cancers arises from tongue and is pathologically identified as squamous cell carcinoma (SCC). 2 Despite tremendous advancement in multimodal therapies against oral cancers over the past decades, the overall 5-year survival rate with these devastating diseases, especially those with advanced diseases, has not been markedly improved. 3 Local relapse and cervical lymph node metastasis are recognized as the most prevalent factors affecting patients' survival. Although many oncogenes and tumor suppressors have been identified as key factors underlying oral tumorigenesis, however, no optimal and commonly accepted biomarkers have been established to facilitate disease diagnosis, ...

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Section: Histopathological Evaluation and Immunohistochemistrymentioning

confidence: 99%

Oncogenic roles of Bmi1 and its therapeutic inhibition by histone deacetylase inhibitor in tongue cancer

Wang

Yuan

et al. 2014

Laboratory Investigation

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“…TAZ gene amplification is also detected in cancers (17)(18)(19)(20)(21). TAZ hyperactivity causes epithelial-mesenchymal transitions (EMT) and provides cancer cells with stemness (22)(23)(24)(25)(26).…”

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confidence: 99%

Screening with a Novel Cell-Based Assay for TAZ Activators Identifies a Compound That Enhances Myogenesis in C2C12 Cells and Facilitates Muscle Repair in a Muscle Injury Model

Yang

Nakagawa

Sarkar

et al. 2014

Molecular and Cellular Biology

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The transcriptional coactivator with a PDZ-binding motif (TAZ) cooperates with various transcriptional factors and plays various roles. Immortalized human mammalian epithelial MCF10A cells form spheres when TAZ is overexpressed and activated. We developed a cell-based assay using sphere formation by TAZ-expressing MCF10A cells as a readout to screen 18,458 chemical compounds for TAZ activators. Fifty compounds were obtained, and 47 were confirmed to activate the TAZ-dependent TEADresponsive reporter activity in HEK293 cells. We used the derived subset of compounds as a TAZ activator candidate minilibrary and searched for compounds that promote myogenesis in mouse C2C12 myoblast cells. In this study, we focused on one compound, IBS008738. IBS008738 stabilizes TAZ, increases the unphosphorylated TAZ level, enhances the association of MyoD with the myogenin promoter, upregulates MyoD-dependent gene transcription, and competes with myostatin in C2C12 cells. TAZ knockdown verifies that the effect of IBS008738 depends on endogenous TAZ in C2C12 cells. IBS008738 facilitates muscle repair in cardiotoxin-induced muscle injury and prevents dexamethasone-induced muscle atrophy. Thus, this cell-based assay is useful to identify TAZ activators with a variety of cellular outputs. Our findings also support the idea that TAZ is a potential therapeutic target for muscle atrophy.

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“…YAP1 integrates the YES-associated protein family and is encoded by the YAP1 gene located on chromosome 11 (11q13) 18. The TAZ protein, which is encoded by the TAZ gene located on chromosome X (Xq28), belongs to the Taffazin family 18.…”

Section: Hippo Pathway's Components and Activationmentioning

confidence: 99%

“…The TAZ protein, which is encoded by the TAZ gene located on chromosome X (Xq28), belongs to the Taffazin family 18. TAZ overexpression was associated with tumourigenesis in tongue squamous cell carcinoma,18 breast cell tumour growth19 and improved growth of thyroid cells in papillary thyroid carcinoma 20. YAP deregulation may contribute to ovarian cancer progression21 and oesophageal squamous cell carcinoma oncogenesis 22.…”

Section: Hippo Pathway's Components and Activationmentioning

confidence: 99%

Hippo pathway deregulation: implications in the pathogenesis of haematological malignancies

et al. 2016

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Overexpression of Hippo pathway effector TAZ in tongue squamous cell carcinoma: correlation with clinicopathological features and patients' prognosis

Cited by 37 publications

References 32 publications

Oncogenic roles of Bmi1 and its therapeutic inhibition by histone deacetylase inhibitor in tongue cancer

Oncogenic roles of Bmi1 and its therapeutic inhibition by histone deacetylase inhibitor in tongue cancer

Screening with a Novel Cell-Based Assay for TAZ Activators Identifies a Compound That Enhances Myogenesis in C2C12 Cells and Facilitates Muscle Repair in a Muscle Injury Model

Hippo pathway deregulation: implications in the pathogenesis of haematological malignancies

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