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10. YAP represses the TEAD–NF-κB complex and inhibits the growth of clear cell renal cell carcinoma.

Author

Li, Zhongbo, Su, Peng, Yu, Miao, Zhang, Xufeng, Xu, Yaning, Jia, Tianwei, Yang, Penghe, Zhang, Chenmiao, Sun, Yanan, Li, Xin, Yang, Huijie, Ding, Yinlu, Zhuang, Ting, Guo, Haiyang, and Zhu, Jian

Subjects
YAP signaling proteins, RENAL cell carcinoma, HIPPO signaling pathway, TRANSCRIPTION factors, CELL culture, CELL growth
Abstract

The Hippo pathway is generally understood to inhibit tumor growth by phosphorylating the transcriptional cofactor YAP to sequester it to the cytoplasm and reduce the formation of YAP-TEAD transcriptional complexes. Aberrant activation of YAP occurs in various cancers. However, we found a tumor-suppressive function of YAP in clear cell renal cell carcinoma (ccRCC). Using cell cultures, xenografts, and patient-derived explant models, we found that the inhibition of upstream Hippo-pathway kinases MST1 and MST2 or expression of a constitutively active YAP mutant impeded ccRCC proliferation and decreased gene expression mediated by the transcription factor NF-κB. Mechanistically, the NF-κB subunit p65 bound to the transcriptional cofactor TEAD to facilitate NF-κB–target gene expression that promoted cell proliferation. However, by competing for TEAD, YAP disrupted its interaction with NF-κB and prompted the dissociation of p65 from target gene promoters, thereby inhibiting NF-κB transcriptional programs. This cross-talk between the Hippo and NF-κB pathways in ccRCC suggests that targeting the Hippo-YAP axis in an atypical manner—that is, by activating YAP—may be a strategy for slowing tumor growth in patients. Editor's summary: The transcriptional cofactor YAP is usually associated with tumor progression. However, Li et al. found that YAP has a tumor-suppressive role in clear cell renal cell carcinoma (ccRCC) by outcompeting another transcription factor for a binding partner. The proliferation of ccRCC cells was driven by the NF-κB subunit p65 in complex with the cofactor TEAD. YAP competed for TEAD binding, displacing p65 and preventing its transcriptional activity. Activating YAP repressed tumor growth in mice, suggesting the potential of this counterintuitive approach to stall primary ccRCC growth in patients. —Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR]

Published
2024
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12. Additional file 5 of RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer

Author

Yang, Huijie, Xue, Min, Su, Peng, Zhou, Yan, Li, Xin, Li, Zhongbo, Xia, Yan, Zhang, Chenmiao, Fu, Mingxi, Zheng, Xiuxia, Luo, Guosheng, Wei, Tian, Wang, Xinxing, Ding, Yinlu, Zhu, Jian, and Zhuang, Ting

Abstract

Additional file 5 Supplementary Fig. 5 A and E Western blot detecting of PD-L1 and RNF31 expression in BT549 and HS578T cells with indicated treatment. B and F RT–qPCR results of PD-L1 mRNA level with indicated treatment in BT549 and HS578T cells. C-D and G-H The cell-membrane localized PD-L1 in BT549 and HS578T cells with indicated treatment were analyzed by Flow cytometry using PD-L1 antibody.

Published
2023
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13. Additional file 1 of RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer

Author

Yang, Huijie, Xue, Min, Su, Peng, Zhou, Yan, Li, Xin, Li, Zhongbo, Xia, Yan, Zhang, Chenmiao, Fu, Mingxi, Zheng, Xiuxia, Luo, Guosheng, Wei, Tian, Wang, Xinxing, Ding, Yinlu, Zhu, Jian, and Zhuang, Ting

Abstract

Additional file 1 Supplementary Fig. 1 A Western blot detecting of RNF31 expression in HS578T cell exposed to indicated methods. B-C Transwell assay (left panel) of HS578T cells. Right panel shows quantification of transwell assay results. Scale bar 100 μm. D-E FACS analysis (left panel) was performed on the HS578T cell to detect the proportion of CD44 + CD24-cells. F-G FACS analysis (left panel) was performed on the HS578T cell to detect the proportion of apoptotic cells. The cells were incubated with PI and Annexin V. Right panel shows quantification of apoptosis proportion. H-I Wound healing assay (left panel) of HS578T cell migration capability following transfected with indicated treatment. J-K Representative images (left panel) of EdU assays in HS578T cell transfected with indicated treatment. EdU-positive cells, red; cell nuclei, blue. Right panel shows quantification of Edu results. Scale bar 100 μm.

Published
2023
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14. Additional file 4 of RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer

Author

Yang, Huijie, Xue, Min, Su, Peng, Zhou, Yan, Li, Xin, Li, Zhongbo, Xia, Yan, Zhang, Chenmiao, Fu, Mingxi, Zheng, Xiuxia, Luo, Guosheng, Wei, Tian, Wang, Xinxing, Ding, Yinlu, Zhu, Jian, and Zhuang, Ting

Abstract

Additional file 4 Supplementary Fig. 4 A-B Western blot detecting of YAP and RNF31 protein localized in cytoplasm and nucleus in the MDAMB231 cell with indicated treatment. Subcellular protein fractionation kit was used for cytoplasm and nucleus separation. Tubulin and Histone3 were engineered to cytoplasm and nucleus controls. Nucleus/Cytoplasm ratio of YAP protein (B). C Representative immunoblots to show the interaction between RNF31 with YAP or TAZ by immunoprecipitation (IP) with RNF31 antibody.

Published
2023
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15. Additional file 2 of RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer

Author

Yang, Huijie, Xue, Min, Su, Peng, Zhou, Yan, Li, Xin, Li, Zhongbo, Xia, Yan, Zhang, Chenmiao, Fu, Mingxi, Zheng, Xiuxia, Luo, Guosheng, Wei, Tian, Wang, Xinxing, Ding, Yinlu, Zhu, Jian, and Zhuang, Ting

Abstract

Additional file 2 Supplementary Fig. 2 A FPKM expression form RNA-Seq in MDAMB231 cell (GSE218406). B Western blot detecting of p38、p-p38 and RNF31 expression in MDAMB231 cell exposed to indicated methods. C Western blot detecting of YAP、YAP P-S127 and RNF31 expression in HS578T cell exposed to indicated methods. D RT–qPCR results of CTGF and CYR61 mRNA expression in HS578T cell transfected with either indicated treatment. E Measurement of TEAD transcriptional activity using luciferase assays using reporters that contain tandem TEAD binding sites in HS578T cell. F-H RT–qPCR results of YAP mRNA expression in indicated cells transfected with either indicated treatment.

Published
2023
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18. TRIM3 Facilitates Estrogen Signaling and Modulates Breast Cancer Cell Progression

Author

Wang, Beibei, primary, Tan, Xiaojing, additional, Wu, Le, additional, Su, Peng, additional, Li, Xin, additional, Yang, Huijie, additional, Cai, Yuqing, additional, Yang, Xiao, additional, Li, Zhongbo, additional, Yan, Cheng, additional, Xia, Yan, additional, zhang, Chenmiao, additional, Niu, Zhiguo, additional, Cao, Qi, additional, Ding, Yinlu, additional, Zhou, Zhipeng, additional, Huang, Qingsong, additional, and Zhuang, Ting, additional

Published
2021
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