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4. MESH1 knockdown triggers proliferation arrest through TAZ repression.

Author

Zhang, Yuning, Zhang, Yang, Lin, Chao-Chieh, Wu, Jianli, Setayeshpour, Yasaman, Coggins, SiAna, Shepard, Caitlin, Macias, Everardo, Kim, Baek, Zhou, Pei, Gordân, Raluca, Chi, Jen-Tsan, Sun, Tianai, and Ding, Chien-Kuang

Subjects
Acetylation, Animals, Cell Proliferation, Guanosine Pentaphosphate, Humans, Mammals, Transcription Factors
Abstract

All organisms are constantly exposed to various stresses, necessitating adaptive strategies for survival. In bacteria, the main stress-coping mechanism is the stringent response triggered by the accumulation of alarmone (p)ppGpp to arrest proliferation and reprogram transcriptome. While mammalian genomes encode MESH1-the homolog of the (p)ppGpp hydrolase SpoT, current knowledge about its function remains limited. We found MESH1 expression tended to be higher in tumors and associated with poor patient outcomes. Consistently, MESH1 knockdown robustly inhibited proliferation, depleted dNTPs, reduced tumor sphere formation, and retarded xenograft growth. These antitumor phenotypes associated with MESH1 knockdown were accompanied by a significantly altered transcriptome, including the repressed expression of TAZ, a HIPPO coactivator, and proliferative gene. Importantly, TAZ restoration mitigated many anti-growth phenotypes of MESH1 knockdown, including proliferation arrest, reduced sphere formation, tumor growth inhibition, dNTP depletion, and transcriptional changes. Furthermore, TAZ repression was associated with the histone hypo-acetylation at TAZ regulatory loci due to the induction of epigenetic repressors HDAC5 and AHRR. Together, MESH1 knockdown in human cells altered the genome-wide transcriptional patterns and arrested proliferation that mimicked the bacterial stringent response through the epigenetic repression of TAZ expression.

Published
2022

12. The effects of glycemic index on prostate cancer progression in a xenograft mouse model

Author

Galván, Gloria Cecilia, primary, Macias, Everardo, additional, Sanders, Sergio, additional, Ramirez-Torres, Adela, additional, Stock, Shannon, additional, You, Sungyong, additional, Riera, Celine E., additional, Tamukong, Patrick, additional, Smith-Warner, Stephanie A., additional, Genkinger, Jeanine M., additional, Luthringer, Daniel J., additional, Freeman, Michael R., additional, and Freedland, Stephen J., additional

Published
2023
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17. Data from 27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6–JAK–STAT3 Signaling in Prostate Cancer Cells

Author

Dambal, Shweta, primary, Alfaqih, Mahmoud, primary, Sanders, Sergio, primary, Maravilla, Erick, primary, Ramirez-Torres, Adela, primary, Galvan, Gloria C., primary, Reis-Sobreiro, Mariana, primary, Rotinen, Mirja, primary, Driver, Lucy M., primary, Behrove, Matthew S., primary, Talisman, Tijana Jovanovic, primary, Yoon, Junhee, primary, You, Sungyong, primary, Turkson, James, primary, Chi, Jen-Tsan, primary, Freeman, Michael R., primary, Macias, Everardo, primary, and Freedland, Stephen J., primary

Published
2023
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18. Figure S7 from 27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6–JAK–STAT3 Signaling in Prostate Cancer Cells

Author

Dambal, Shweta, primary, Alfaqih, Mahmoud, primary, Sanders, Sergio, primary, Maravilla, Erick, primary, Ramirez-Torres, Adela, primary, Galvan, Gloria C., primary, Reis-Sobreiro, Mariana, primary, Rotinen, Mirja, primary, Driver, Lucy M., primary, Behrove, Matthew S., primary, Talisman, Tijana Jovanovic, primary, Yoon, Junhee, primary, You, Sungyong, primary, Turkson, James, primary, Chi, Jen-Tsan, primary, Freeman, Michael R., primary, Macias, Everardo, primary, and Freedland, Stephen J., primary

Published
2023
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19. Supplemental Materials and Methods, Supplementary Tables 1 and 2 from 27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6–JAK–STAT3 Signaling in Prostate Cancer Cells

Author

Dambal, Shweta, primary, Alfaqih, Mahmoud, primary, Sanders, Sergio, primary, Maravilla, Erick, primary, Ramirez-Torres, Adela, primary, Galvan, Gloria C., primary, Reis-Sobreiro, Mariana, primary, Rotinen, Mirja, primary, Driver, Lucy M., primary, Behrove, Matthew S., primary, Talisman, Tijana Jovanovic, primary, Yoon, Junhee, primary, You, Sungyong, primary, Turkson, James, primary, Chi, Jen-Tsan, primary, Freeman, Michael R., primary, Macias, Everardo, primary, and Freedland, Stephen J., primary

Published
2023
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21. Data from CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer

Author

Alfaqih, Mahmoud A., primary, Nelson, Erik R., primary, Liu, Wen, primary, Safi, Rachid, primary, Jasper, Jeffery S., primary, Macias, Everardo, primary, Geradts, Joseph, primary, Thompson, J. Will, primary, Dubois, Laura G., primary, Freeman, Michael R., primary, Chang, Ching-yi, primary, Chi, Jen-Tsan, primary, McDonnell, Donald P., primary, and Freedland, Stephen J., primary

Published
2023
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22. Supplementary Figure S3 from CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer

Author

Alfaqih, Mahmoud A., primary, Nelson, Erik R., primary, Liu, Wen, primary, Safi, Rachid, primary, Jasper, Jeffery S., primary, Macias, Everardo, primary, Geradts, Joseph, primary, Thompson, J. Will, primary, Dubois, Laura G., primary, Freeman, Michael R., primary, Chang, Ching-yi, primary, Chi, Jen-Tsan, primary, McDonnell, Donald P., primary, and Freedland, Stephen J., primary

Published
2023
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23. Supplementary Materials and Methods from CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer

Author

Alfaqih, Mahmoud A., primary, Nelson, Erik R., primary, Liu, Wen, primary, Safi, Rachid, primary, Jasper, Jeffery S., primary, Macias, Everardo, primary, Geradts, Joseph, primary, Thompson, J. Will, primary, Dubois, Laura G., primary, Freeman, Michael R., primary, Chang, Ching-yi, primary, Chi, Jen-Tsan, primary, McDonnell, Donald P., primary, and Freedland, Stephen J., primary

Published
2023
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24. Supplementary Table S1-S3 from CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer

Author

Alfaqih, Mahmoud A., primary, Nelson, Erik R., primary, Liu, Wen, primary, Safi, Rachid, primary, Jasper, Jeffery S., primary, Macias, Everardo, primary, Geradts, Joseph, primary, Thompson, J. Will, primary, Dubois, Laura G., primary, Freeman, Michael R., primary, Chang, Ching-yi, primary, Chi, Jen-Tsan, primary, McDonnell, Donald P., primary, and Freedland, Stephen J., primary

Published
2023
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33. Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

Author

Schirmer, Amelia U., primary, Driver, Lucy M., additional, Zhao, Megan T., additional, Wells, Carrow I., additional, Pickett, Julie E., additional, O’Bryne, Sean N., additional, Eduful, Benjamin J., additional, Yang, Xuan, additional, Howard, Lauren, additional, You, Sungyong, additional, Devi, Gayathri R., additional, DiGiovanni, John, additional, Freedland, Stephen J., additional, Chi, Jen-Tsan, additional, Drewry, David H., additional, and Macias, Everardo, additional

Published
2022
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