The Emerging Role of YAP/TAZ in Tumor Immunity

Pan, Zhaoji; Tian, Ye; Cao, Chengsong; Niu, Guoping

doi:10.1158/1541-7786.mcr-19-0375

Cited by 76 publications

(60 citation statements)

References 146 publications

(179 reference statements)

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“…Among the plethora of diverse functions for YAP1 and WWTR1 evidence for their critical roles in mediating immune response have recently emerged ( Geng et al, 2017 ; Janse van Rensburg et al, 2018 ; Pan et al, 2019 ). Specifically, WWTR1 but not YAP1 was shown to be essential for T H 17 cell differentiation ( Geng et al, 2017 ), and constitutively active WWTR1 (TAZ-S89A) was shown to induce PD-L1 expression to a much greater extent than YAP1 (YAP1-S127A) ( Janse van Rensburg et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway

Chai

Yee

Price

et al. 2020

eLife

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New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identified OSCC-related cancer genes are non-essential and could have limited therapeutic value, while other fitness genes warrant further investigation for their potential as therapeutic targets. We validate a distinctive dependency on YAP1 and WWTR1 of the Hippo pathway, where the lost-of-fitness effect of one paralog can be compensated only in a subset of lines. We also discover that OSCCs with WWTR1 dependency signature are significantly associated with biomarkers of favourable response towards immunotherapy. In summary, we have delineated the genetic vulnerabilities of OSCC, enabling the prioritization of therapeutic targets for further exploration, including the targeting of YAP1 and WWTR1.

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Section: Resultsmentioning

confidence: 99%

Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway

Chai

Yee

Price

et al. 2020

eLife

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“…To establish tumors, cancer cells need to escape from immune surveillance. Recently, it has been demonstrated that YAP/TAZ is involved in immune evasion as well as the resistance to immune checkpoint inhibitors (64). For instance, YAP/TAZ has been shown to upregulate chemokine CXCL5 and CCL2, resulting in the recruitment of immune suppressive myeloid-derived suppressor cells (MDSC) and M2 macrophages, respectively (65,66).…”

Section: The Role Of Yap/taz In Cancer Progressionmentioning

confidence: 99%

A Potential Role of YAP/TAZ in the Interplay Between Metastasis and Metabolic Alterations

Yamaguchi

Taouk

2020

Front. Oncol.

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Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) are the downstream effectors of the Hippo signaling pathway that play a crucial role in various aspects of cancer progression including metastasis. Metastasis is the multistep process of disseminating cancer cells in a body and responsible for the majority of cancer-related death. Emerging evidence has shown that cancer cells reprogram their metabolism to gain proliferation, invasion, migration, and anti-apoptotic abilities and adapt to various environment during metastasis. Moreover, it has increasingly been recognized that YAP/TAZ regulates cellular metabolism that is associated with the phenotypic changes, and recent studies suggest that the YAP/TAZ-mediated metabolic alterations contribute to metastasis. In this review, we will introduce the latest knowledge of YAP/TAZ regulation and function in cancer metastasis and metabolism, and discuss possible links between the YAP/TAZ-mediated metabolic reprogramming and metastasis.

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“…Thus, further investigation is required to elucidate whether atorvastatin efficiently inhibits CCA cell growth in mice with hypercholesterolemia. Third, inhibition of oncogenic YAP activity also alters the tumor microenvironment, including tumor-associated fibrosis, angiogenesis, and immunity [ 43 ]. Additional analysis of these multifunctional effects of statins using the present model is required.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin Augments Gemcitabine-Mediated Anti-Cancer Effects by Inhibiting Yes-Associated Protein in Human Cholangiocarcinoma Cells

Kitagawa

Moriya

Kaji

et al. 2020

IJMS

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Cholangiocarcinoma (CCA) is associated with high mortality rates because of its resistance to conventional gemcitabine-based chemotherapy. Hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins) reportedly exert anti-cancer effects in CCA and lower the risk of CCA; however, the underlying mechanism of these effects remains unclear. The proliferative and oncogenic activities of the transcriptional co-activator Yes-associated protein (YAP) are driven by its association with the TEA domain (TEAD) of transcription factors; thereby, upregulating genes that promote cell growth, inhibit apoptosis, and confer chemoresistance. This study investigated the effects of atorvastatin in combination with gemcitabine on the progression of human CCA associated with YAP oncogenic regulation. Both atorvastatin and gemcitabine concentration-dependently suppressed the proliferation of HuCCT-1 and KKU-M213 human CCA cells. Moreover, both agents induced cellular apoptosis by upregulating the pro-apoptotic marker BAX and downregulating the anti-apoptotic markers MCL1 and BCL2. Atorvastatin also significantly decreased the mRNA expression of the TEAD target genes CTGF, CYR61, ANKRD1, and MFAP5 in both CCA cell lines. A xenograft tumor growth assay indicated that atorvastatin and gemcitabine potently repressed human CCA cell-derived subcutaneous tumor growth by inhibiting YAP nuclear translocation and TEAD transcriptional activation. Notably, the anti-cancer effects of the individual agents were significantly enhanced in combination. These results indicate that gemcitabine plus atorvastatin could serve as a potential novel treatment option for CCA.

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The Emerging Role of YAP/TAZ in Tumor Immunity

Cited by 76 publications

References 146 publications

Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway

Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway

A Potential Role of YAP/TAZ in the Interplay Between Metastasis and Metabolic Alterations

Atorvastatin Augments Gemcitabine-Mediated Anti-Cancer Effects by Inhibiting Yes-Associated Protein in Human Cholangiocarcinoma Cells

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