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186 results on '"Luo, Weibo"'

1. Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance.

Author

Carney, Stephen, Banerjee, Kaushik, Mujeeb, Anzar, Zhu, Brandon, Haase, Santiago, Varela, Maria, Kadiyala, Padma, Tronrud, Claire, Zhu, Ziwen, Mukherji, Devarshi, Gorla, Preethi, Sun, Yilun, Tagett, Rebecca, Núñez, Felipe, Luo, Maowu, Luo, Weibo, Ljungman, Mats, Liu, Yayuan, Xia, Ziyun, Schwendeman, Anna, Qin, Tingting, Sartor, Maureen, Cahill, Daniel, Lowenstein, Pedro, Castro, Maria, and Costello, Joseph

Subjects
Humans, Isocitrate Dehydrogenase, MYND Domains, Epigenesis, Genetic, Nuclear Proteins, Poly(ADP-ribose) Polymerase Inhibitors, Transcription Factors, Glioma, Cell Cycle Proteins
Abstract

PURPOSE: Mutant isocitrate dehydrogenase 1 (mIDH1) alters the epigenetic regulation of chromatin, leading to a hypermethylation phenotype in adult glioma. This work focuses on identifying gene targets epigenetically dysregulated by mIDH1 to confer therapeutic resistance to ionizing radiation (IR). EXPERIMENTAL DESIGN: We evaluated changes in the transcriptome and epigenome in a radioresistant mIDH1 patient-derived glioma cell culture (GCC) following treatment with an mIDH1-specific inhibitor, AGI-5198. We identified Zinc Finger MYND-Type Containing 8 (ZMYND8) as a potential target of mIDH1 reprogramming. We suppressed ZMYND8 expression by shRNA knockdown and genetic knockout (KO) in mIDH1 glioma cells and then assessed cellular viability to IR. We assessed the sensitivity of mIDH1 GCCS to pharmacologic inhibition of ZMYND8-interacting partners: HDAC, BRD4, and PARP. RESULTS: Inhibition of mIDH1 leads to an upregulation of gene networks involved in replication stress. We found that the expression of ZMYND8, a regulator of DNA damage response, was decreased in three patient-derived mIDH1 GCCs after treatment with AGI-5198. Knockdown of ZMYND8 expression sensitized mIDH1 GCCs to radiotherapy marked by decreased cellular viability. Following IR, mIDH1 glioma cells with ZMYND8 KO exhibit significant phosphorylation of ATM and sustained γH2AX activation. ZMYND8 KO mIDH1 GCCs were further responsive to IR when treated with either BRD4 or HDAC inhibitors. PARP inhibition further enhanced the efficacy of radiotherapy in ZMYND8 KO mIDH1 glioma cells. CONCLUSIONS: These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma. See related commentary by Sachdev et al., p. 1648.

Published
2023

3. ZMYND8 protects breast cancer stem cells against oxidative stress and ferroptosis through activation of NRF2

Author

Luo, Maowu, Bao, Lei, Xue, Yuanyuan, Zhu, Ming, Kumar, Ashwani, Xing, Chao, Wang, Jennifer E., Wang, Yingfei, and Luo, Weibo

Subjects
Thermo Fisher Scientific Inc., STEMCELL Technologies Inc., Scientific equipment and supplies industry, Stem cells, Antioxidants, Diagnostic reagents industry, Oxidative stress, Genetic transcription, Breast cancer, Health care industry
Abstract

Breast cancer stem cells (BCSCs) mitigate oxidative stress to maintain their viability and plasticity. However, the regulatory mechanism of oxidative stress in BCSCs remains unclear. We recently found that the histone reader ZMYND8 was upregulated in BCSCs. Here, we showed that ZMYND8 reduced ROS and iron to inhibit ferroptosis in aldehyde dehydrogenase-high ([ALDH.sup.hi]) BCSCs, leading to BCSC expansion and tumor initiation in mice. The underlying mechanism involved a two-fold posttranslational regulation of nuclear factor erythroid 2-related factor 2 (NRF2). ZMYND8 increased stability of NRF2 protein through KEAP1 silencing. On the other hand, ZMYND8 interacted with and recruited NRF2 to the promoters of antioxidant genes to enhance gene transcription in mammospheres. NRF2 phenocopied ZMYND8 to enhance BCSC stemness and tumor initiation by inhibiting ROS and ferroptosis. Loss of NRF2 counteracted ZMYND8's effects on antioxidant genes and ROS in mammospheres. Interestingly, ZMYND8 expression was directly controlled by NRF2 in mammospheres. Collectively, these findings uncover a positive feedback loop that amplifies the antioxidant defense mechanism sustaining BCSC survival and stemness., Introduction Breast cancer stem cells (BCSCs) are defined as a subpopulation of tumor cells with capability of self renewal and long-term maintenance of breast tumors and are responsible for breast [...]

Published
2024
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4. Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma

Author

Hu, Lianxin, Zhang, Yanfeng, Guo, Lei, Zhong, Hua, Xie, Ling, Zhou, Jin, Liao, Chengheng, Yao, Hongwei, Fang, Jun, Liu, Hongyi, Zhang, Cheng, Zhang, Hui, Zhu, Xiaoqiang, Luo, Maowu, von Kriegsheim, Alex, Li, Bufan, Luo, Weibo, Zhang, Xuewu, Chen, Xian, Mendell, Joshua T., Xu, Lin, Kapur, Payal, Baldwin, Albert S., Brugarolas, James, and Zhang, Qing

Published
2024
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5. Histone H3 proline 16 hydroxylation regulates mammalian gene expression

Author

Liu, Xijuan, Wang, Jun, Boyer, Joshua A., Gong, Weida, Zhao, Shuai, Xie, Ling, Wu, Qiong, Zhang, Cheng, Jain, Kanishk, Guo, Yiran, Rodriguez, Javier, Li, Mingjie, Uryu, Hidetaka, Liao, Chengheng, Hu, Lianxin, Zhou, Jin, Shi, Xiaobing, Tsai, Yi-Hsuan, Yan, Qin, Luo, Weibo, Chen, Xian, Strahl, Brian D., von Kriegsheim, Alex, Zhang, Qi, Wang, Gang Greg, Baldwin, Albert S., and Zhang, Qing

Published
2022
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6. SAP30 promotes breast tumor progression by bridging the transcriptional corepressor SIN3 complex and MLL1

Author

Bao, Lei, Kumar, Ashwani, Zhu, Ming, Peng, Yan, Xing, Chao, Wang, Jennifer E., Wang, Yingfei, and Luo, Weibo

Subjects
Epigenetic inheritance -- Health aspects -- Physiological aspects, Breast cancer -- Development and progression -- Genetic aspects, Transcription factors -- Physiological aspects -- Health aspects, Health care industry
Abstract

SAP30 is a core subunit of the transcriptional corepressor SIN3 complex, but little is known about its role in gene regulation and human cancer. Here, we show that SAP30 was a nonmutational oncoprotein upregulated in more than 50% of human breast tumors and correlated with unfavorable outcomes in patients with breast cancer. In various breast cancer mouse models, we found that SAP30 promoted tumor growth and metastasis through its interaction with SIN3A/3B. Surprisingly, the canonical gene silencing role was not essential for SAP30's tumor-promoting actions. SAP30 enhanced chromatin accessibility and RNA polymerase II occupancy at promoters in breast cancer cells, acting as a coactivator for genes involved in cell motility, angiogenesis, and lymphangiogenesis, thereby driving tumor progression. Notably, SAP30 formed a homodimer with 1 subunit binding to SIN3A and another subunit recruiting MLL1 through specific Phe186/200 residues within its transactivation domain. MLL1 was required for SAP30-mediated transcriptional coactivation and breast tumor progression. Collectively, our findings reveal that SAP30 represents a transcriptional dependency in breast cancer., Introduction Breast cancer is the most common malignant disease in women, with many patients dying of metastasis. The development of breast cancer toward distant metastasis is a harsh process, wherein [...]

Published
2023
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7. Supplementary Figures S1-S17 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2024
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8. Supplementary Table S2 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2024
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9. Data from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2024
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10. Supplementary Methods S1 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2024
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14. Hypoxia Mediates Tumor Malignancy and Therapy Resistance

Author

Luo, Weibo, Wang, Yingfei, COHEN, IRUN R., Editorial Board Member, LAJTHA, ABEL, Editorial Board Member, LAMBRIS, JOHN D., Editorial Board Member, PAOLETTI, RODOLFO, Editorial Board Member, REZAEI, NIMA, Editorial Board Member, and Gilkes, Daniele M., editor

Published
2019
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17. AIF3 splicing switch triggers neurodegeneration

Author

Liu, Shuiqiao, Zhou, Mi, Ruan, Zhi, Wang, Yanan, Chang, Calvin, Sasaki, Masayuki, Rajaram, Veena, Lemoff, Andrew, Nambiar, Kalyani, Wang, Jennifer E., Hatanpaa, Kimmo J., Luo, Weibo, Dawson, Ted M., Dawson, Valina L., and Wang, Yingfei

Published
2021
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19. Supplementary Table S1 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2023
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20. Data from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2023
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21. Supplementary Methods S1 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2023
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22. Supplementary Figures S1-S17 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance

Author

Carney, Stephen V., primary, Banerjee, Kaushik, primary, Mujeeb, Anzar, primary, Zhu, Brandon, primary, Haase, Santiago, primary, Varela, Maria L., primary, Kadiyala, Padma, primary, Tronrud, Claire E., primary, Zhu, Ziwen, primary, Mukherji, Devarshi, primary, Gorla, Preethi, primary, Sun, Yilun, primary, Tagett, Rebecca, primary, Núñez, Felipe J., primary, Luo, Maowu, primary, Luo, Weibo, primary, Ljungman, Mats, primary, Liu, Yayuan, primary, Xia, Ziyun, primary, Schwendeman, Anna, primary, Qin, Tingting, primary, Sartor, Maureen A., primary, Costello, Joseph F., primary, Cahill, Daniel P., primary, Lowenstein, Pedro R., primary, and Castro, Maria G., primary

Published
2023
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26. ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis

Author

Chen, Yan, Zhang, Bo, Bao, Lei, Jin, Lai, Yang, Mingming, Peng, Yan, Kumar, Ashwani, Wang, Jennifer E., Wang, Chenliang, Zou, Xuan, Xing, Chao, Wang, Yingfei, and Luo, Weibo

Subjects
Epigenetic inheritance -- Health aspects, Zinc finger proteins -- Health aspects -- Genetic aspects, Breast cancer -- Genetic aspects -- Development and progression, Cancer metastasis -- Genetic aspects -- Development and progression, Transcription factors -- Health aspects, Health care industry
Abstract

Altered epigenetic reprogramming contributes to breast cancer progression and metastasis. How the epigenetic reader mediates breast cancer progression remains poorly understood. Here, we showed that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) is induced by HIF-1 and HIF-2 in breast cancer cells and also upregulated in human breast tumors, and is correlated with poor survival of patients with breast cancer. Genetic deletion of ZMYND8 decreases breast cancer cell colony formation, migration, and invasion in vitro, and inhibits breast tumor growth and metastasis to the lungs in mice. The ZMYND8's oncogenic effect in breast cancer requires HIF-1 and HIF-2. We further showed that ZMYND8 interacts with HIF-1[alpha] and HIF-2[alpha] and enhances elongation of the global HIF-induced oncogenic genes by increasing recruitment of BRD4 and subsequent release of paused RNA polymerase II in breast cancer cells. ZMYND8 acetylation at lysines 1007 and 1034 by p300 is required for HIF activation and breast cancer progression and metastasis. These findings uncover a primary epigenetic mechanism of HIF activation and HIF-mediated breast cancer progression, and discover a possible molecular target for the diagnosis and treatment of breast cancer., Introduction Metastasis is a major clinical obstacle to curative cancer therapy and is responsible for about 90% of breast cancer-related deaths in women. The development of a benign and nonmalignant [...]

Published
2018
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28. Data from Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma

Author

Zhang, Bo, primary, Peng, Hui, primary, Zhou, Mi, primary, Bao, Lei, primary, Wang, Chenliang, primary, Cai, Feng, primary, Zhang, Hongxia, primary, Wang, Jennifer E., primary, Niu, Yanling, primary, Chen, Yan, primary, Wang, Yijie, primary, Hatanpaa, Kimmo J., primary, Copland, John A., primary, DeBerardinis, Ralph J., primary, Wang, Yingfei, primary, and Luo, Weibo, primary

Published
2023
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31. Supplementary Data from Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma

Author

Zhang, Bo, primary, Peng, Hui, primary, Zhou, Mi, primary, Bao, Lei, primary, Wang, Chenliang, primary, Cai, Feng, primary, Zhang, Hongxia, primary, Wang, Jennifer E., primary, Niu, Yanling, primary, Chen, Yan, primary, Wang, Yijie, primary, Hatanpaa, Kimmo J., primary, Copland, John A., primary, DeBerardinis, Ralph J., primary, Wang, Yingfei, primary, and Luo, Weibo, primary

Published
2023
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35. Abstract P4-08-23: ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer

Author

Liao, Chengheng, primary, Fang, Wentong, additional, Shi, Rachel, additional, Simon, Jeremy, additional, Ptacek, Travis, additional, Zurlo, Giada, additional, Ye, Youqiong, additional, Han, Leng, additional, Fan, Cheng, additional, Bao, Lei, additional, Ortiz, Christopher Llynard, additional, Lin, Hong-Rui, additional, Manocha, Ujjawal, additional, Luo, Weibo, additional, Peng, Yan, additional, Kim, William Y, additional, Yang, Lee-Wei, additional, and Zhang, Qing, additional

Published
2023
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38. ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells

Author

Luo, Maowu, primary, Bao, Lei, additional, Chen, Yan, additional, Xue, Yuanyuan, additional, Wang, Yong, additional, Zhang, Bo, additional, Wang, Chenliang, additional, Corley, Chase D., additional, McDonald, Jeffrey G., additional, Kumar, Ashwani, additional, Xing, Chao, additional, Fang, Yisheng, additional, Nelson, Erik R., additional, Wang, Jennifer E., additional, Wang, Yingfei, additional, and Luo, Weibo, additional

Published
2022
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40. Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma

Author

Zhang, Bo, primary, Peng, Hui, additional, Zhou, Mi, additional, Bao, Lei, additional, Wang, Chenliang, additional, Cai, Feng, additional, Zhang, Hongxia, additional, Wang, Jennifer E., additional, Niu, Yanling, additional, Chen, Yan, additional, Wang, Yijie, additional, Hatanpaa, Kimmo J., additional, Copland, John A., additional, DeBerardinis, Ralph J., additional, Wang, Yingfei, additional, and Luo, Weibo, additional

Published
2022
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43. ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer

Author

Fang, Wentong, primary, Liao, Chengheng, primary, Shi, Rachel, additional, Simon, Jeremy M, additional, Ptacek, Travis S, additional, Zurlo, Giada, additional, Ye, Youqiong, additional, Han, Leng, additional, Fan, Cheng, additional, Bao, Lei, additional, Ortiz, Christopher Llynard, additional, Lin, Hong-Rui, additional, Manocha, Ujjawal, additional, Luo, Weibo, additional, Peng, Yan, additional, Kim, William Y, additional, Yang, Lee-Wei, additional, and Zhang, Qing, additional

Published
2021
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44. Author response: ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer

Author

Fang, Wentong, primary, Liao, Chengheng, primary, Shi, Rachel, additional, Simon, Jeremy M, additional, Ptacek, Travis S, additional, Zurlo, Giada, additional, Ye, Youqiong, additional, Han, Leng, additional, Fan, Cheng, additional, Bao, Lei, additional, Ortiz, Christopher Llynard, additional, Lin, Hong-Rui, additional, Manocha, Ujjawal, additional, Luo, Weibo, additional, Peng, Yan, additional, Kim, William Y, additional, Yang, Lee-Wei, additional, and Zhang, Qing, additional

Published
2021
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