YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer

Shen, Jie; Huang, Qiu‐An; Jia, Wentao; Feng, Sheng-Ya; Liu, Liang; Li, Xiaolan; Tao, Deding; Xie, Daxing

doi:10.1038/s41388-022-02344-4

Cited by 20 publications

(16 citation statements)

References 66 publications

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“…5A ), compared with breast cancer or bladder cancer cells, in which the YAP/TAZ-TEAD4 complex has been reported to drive malignant phenotypes (fig. S16, A and B) ( 34 , 35 ). Furthermore, we performed gel filtration chromatography analysis and found that low levels of TEAD4 formed complexes with YAP/TAZ in NPC ( Fig.…”

Section: Resultsmentioning

confidence: 99%

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

Wang

Wei

et al. 2023

Sci. Adv.

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The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1–associating protein)–mediated TEAD4 m 6 A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

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Section: Resultsmentioning

confidence: 99%

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

Wang

Wei

et al. 2023

Sci. Adv.

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“…Next, we examined whether YAP could regulate CIN in vitro. As previously reported, YAP protein was relatively highly expressed in MDA-MB-231, and low show low expression in MCF7 and MCF10A 24 , thus these three cell lines were selected for further study. Firstly, we knocked out endogenous YAP via CRISPR/Cas9 in MDA-MB-231 cells and stable overexpressing YAP in MCF7 and MCF10A cells (Fig.…”

Section: Yap Induces Cin Formation and Aberrant Mitosis In Breast Cancermentioning

confidence: 92%

YAP promotes chromosomal instability by transcriptionally activating AJUBA through its super enhancer in breast cancer

Huang,

Zhang,

Meng

et al. 2024

Preprint

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SummaryChromosomal instability (CIN) has been proven to be a fundamental property of cancer and a key underlying mechanism of tumorigenesis and progression. Still, relatively few studies have revealed the mechanism of this process. In this research, we identified the core Hippo component, YAP, played a crucial role in CIN formation in breast cancer. Using public ChIP-seq data and bioinformatic analysis, we found YAP could transcriptionally induce spindle assembly checkpoint, AJUBA, via TEAD, then activate AJUBA-AURKA signaling. Abolish AJUBA-AURKA axis could reverse YAP-induced CIN formation and aberrant mitosis. Mechanically, YAP/TEAD complex could accumulate to the super enhancer region of AJUBA, thus significantly induced its expression, and subsequently promoted AURKA auto-phosphorylating. These findings revealed a novel cross-talk between Hippo and AJUBA-AURKA signaling, and provided a new insight in CIN formation in breast cancer.

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“…Invadopodia assays were performed following Jie Shen's study 16 . In brief, 20% nitric acid‐pretreated coverslips (12 mm) were washed and incubated with 50 μg/mL poly‐L‐lysine.…”

Section: Methodsmentioning

confidence: 99%

“…Invadopodia assays were performed following Jie Shen's study. 16 In brief, 20% nitric acid-pretreated coverslips (12 mm) were washed and incubated with 50 μg/mL poly-L-lysine. Then, coverslips were incubated with enough 0.5% glutaraldehyde and inverted onto gelatin with a droplet size of 30 μL.…”

Section: Invadopodia Assaymentioning

confidence: 99%

Stiffness promotes cell migration, invasion, and invadopodia in nasopharyngeal carcinoma by regulating the WT‐CTTN level

Bao,

Zhong,

Zhang

et al. 2024

Cancer Science

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Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness‐induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT‐CTTN or splice variants (SV1‐CTTN or SV2‐CTTN) regulate matrix stiffness‐induced malignant phenotype is largely unknown. We proved that alteration of WT‐CTTN expression modulated matrix stiffness‐induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT‐CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2‐WT‐CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.

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YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer

Cited by 20 publications

References 66 publications

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

YAP promotes chromosomal instability by transcriptionally activating AJUBA through its super enhancer in breast cancer

Stiffness promotes cell migration, invasion, and invadopodia in nasopharyngeal carcinoma by regulating the WT‐CTTN level

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