VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer

Zhang, Yinglong; Shen, He; Withers, Henry G.; Yang, Nuo; Denson, Kayla E.; Mussell, Ashley L.; Truskinovsky, Alexander M.; Fan, Qingyu; Gelman, Irwin H.; Frangou, Costa; Zhang, Jianmin

doi:10.1038/s41598-017-06227-7

Cited by 47 publications

(56 citation statements)

References 51 publications

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“…One limitation of our model is that despite the specificity of the TBDs they could cause additional nuclear effects that are not mediated by YAP1/TAZ, particularly the TBD of VGLL4. It has been shown in numerous studies that the main function of VGLL4 in cells is to block the binding of YAP1/TAZ to TEAD transcription factors 21,[38][39][40][41][42] , indicating that TBD-VGLL4 should not have any additional effects than to potentiate endogenous VGLL4-mediated TEAD inhibition. In addition, VGLL4 knockout mice have no reported phenotype on skin development 42 , suggesting that blockage of VGLL4 in keratinocytes might not have any functional consequences.…”

Section: Discussionmentioning

confidence: 99%

YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity

et al. 2020

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The Hippo TEAD-transcriptional regulators YAP1 and TAZ are central for cell renewal and cancer growth; however, the specific downstream gene networks involved in their activity are not completely understood. Here we introduce TEADi, a genetically encoded inhibitor of the interaction of YAP1 and TAZ with TEAD, as a tool to characterize the transcriptional networks and biological effects regulated by TEAD transcription factors. Blockage of TEAD activity by TEADi in human keratinocytes and mouse skin leads to reduced proliferation and rapid activation of differentiation programs. Analysis of gene networks affected by TEADi and YAP1/TAZ knockdown identifies KLF4 as a central transcriptional node regulated by YAP1/ TAZ-TEAD in keratinocyte differentiation. Moreover, we show that TEAD and KLF4 can regulate the activity of each other, indicating that these factors are part of a transcriptional regulatory loop. Our study establishes TEADi as a resource for studying YAP1/TAZ-TEAD dependent effects.

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Section: Discussionmentioning

confidence: 99%

YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity

et al. 2020

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“…Accumulating evidence has implicated that YAP serves an important and multifaceted role in cancer progression, including gastric cancer, pediatric cancer and breast cancer (7)(8)(9)(10). YAP also been demonstrated to be overexpressed in various types of solid tumors, including gastric cancer, pediatric cancer and breast cancer, and its overexpression is associated with tumor initiation, invasion and metastasis (9,11,12).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of YAP inhibits proliferation, invasion and increases cisplatin sensitivity in human hepatocellular carcinoma cells

Wang¹,

Wu²,

Zhong³

2018

Oncol Lett

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Abstract. Yes-associated protein (YAP) serves an essential role in tumorigenesis. However, the potential role and the molecular mechanism underlying the effect of YAP on hepatocellular carcinoma (HCC) cells have not been elucidated. In the current study, it was revealed that YAP expression was increased significantly in HCC cancer tissues and its overexpression was associated with tumor differentiation. The silencing of YAP by small interferring RNA led to the inhibition of HCC cell growth, which was associated with the promotion of apoptosis. The silencing of YAP also decreased the invasive potential of HCC cells and the activity of the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway. Furthermore, silencing of YAP increased the chemosensitivity of HCC cells to cisplatin (CDDP) through inactivation of the PI3K/AKT signaling pathway. In vivo studies using PDTX model suggested a promotive role for YAP in the growth of HCC and knockdown of YAP increased the anti-tumor activity of CDDP. Taken together, these results revealed that YAP is overexpressed in HCC, and promotes proliferation, invasion and drug resistance of HCC cells. Inhibition of YAP, alone or in combination with traditional chemotherapy, may effectively combat HCC.

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“…The K562 cell line was used to demonstrate the immunolabelling of DCTPP1 (Song et al , ) and survivin (Schmidt et al , ), and showed moderate cytoplasmic levels of both. MDA‐MB‐231 cell line was used to demonstrate we could immunolabel DCTPP1 (Song et al , ), while MDA‐MB‐468 was chosen as an immunolabelling control for VGLL4 (Zhang et al , ), but both were negative for the detection of these antigens. Of note VGLL4 was not found in any cell line, MDA‐MB‐231 and MDA‐MB‐468 did not express DCTPP1 or survivin, while each had transcripts from these antigens that were detectable by qPCR.…”

Section: Resultsmentioning

confidence: 99%

Serum profiling identifies ibrutinib as a treatment option for young adults with B‐cell acute lymphoblastic leukaemia

et al. 2020

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Acute lymphoblastic leukaemia (ALL) is a haematological malignancy that is characterized by the uncontrolled proliferation of immature lymphocytes. 80% of cases occur in children where ALL is well understood and treated. However it has a devastating affects on adults, where multi-agent chemotherapy is the standard of care with allogeneic stem cell transplantation for those who are eligible. New treatments are required to extend remission and prevent relapse to improve patient survival rates. We used serum profiling to compare samples from presentation adult B-ALL patients with age-and sex-matched healthy volunteer (HV) sera and identified 69 differentially recognised antigens (P ≤ 0Á02). BMX, DCTPP1 and VGLL4 showed no differences in transcription between patients and healthy donors but were each found to be present at higher levels in B-ALL patient samples than HVs by ICC. BMX plays a crucial role in the Bruton's Tyrosine Kinase (BTK) pathway which is bound by the BTK inhibitor, ibrutinib, suggesting adult B-ALL would also be a worthy target patient group for future clinical trials. We have shown the utility of proto-array analysis of B-ALL patient sera, predominantly from young adults, to help characterise the B-ALL immunome and identified a new target patient population for existing small molecule therapy.

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VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer

Cited by 47 publications

References 51 publications

YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity

YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity

Downregulation of YAP inhibits proliferation, invasion and increases cisplatin sensitivity in human hepatocellular carcinoma cells

Serum profiling identifies ibrutinib as a treatment option for young adults with B‐cell acute lymphoblastic leukaemia

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