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1,922 results on '"DePinho, Ronald A."'

1. Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer

Author

Saito, Yohei, Xiao, Yi, Yao, Jun, Li, Yunhai, Liu, Wendao, Yuzhalin, Arseniy E., Shyu, Yueh-Ming, Li, Hongzhong, Yuan, Xiangliang, Li, Ping, Zhang, Qingling, Li, Ziyi, Wei, Yongkun, Yin, Xuedong, Zhao, Jun, Kariminia, Seyed M., Wu, Yao-Chung, Wang, Jinyang, Yang, Jun, Xia, Weiya, Sun, Yutong, Jho, Eek-hoon, Chiao, Paul J., Hwang, Rosa F., Ying, Haoqiang, Wang, Huamin, Zhao, Zhongming, Maitra, Anirban, Hung, Mien-Chie, DePinho, Ronald A., and Yu, Dihua

Published
2024
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4. Histone demethylase KDM5D upregulation drives sex differences in colon cancer

Author

Li, Jiexi, Lan, Zhengdao, Liao, Wenting, Horner, James W., Xu, Xueping, Liu, Jielin, Yoshihama, Yohei, Jiang, Shan, Shim, Hong Seok, Slotnik, Max, LaBella, Kyle A., Wu, Chang-Jiun, Dunner, Jr., Kenneth, Hsu, Wen-Hao, Lee, Rumi, Khanduri, Isha, Terranova, Christopher, Akdemir, Kadir, Chakravarti, Deepavali, Shang, Xiaoying, Spring, Denise J., Wang, Y. Alan, and DePinho, Ronald A.

Published
2023
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5. Unique challenges for glioblastoma immunotherapy—discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank

Author

Chuntova, Pavlina, Chow, Frances, Watchmaker, Payal B, Galvez, Mildred, Heimberger, Amy B, Newell, Evan W, Diaz, Aaron, DePinho, Ronald A, Li, Ming O, Wherry, E John, Mitchell, Duane, Terabe, Masaki, Wainwright, Derek A, Berzofsky, Jay A, Herold-Mende, Christel, Heath, James R, Lim, Michael, Margolin, Kim A, Chiocca, E Antonio, Kasahara, Noriyuki, Ellingson, Benjamin M, Brown, Christine E, Chen, Yvonne, Fecci, Peter E, Reardon, David A, Dunn, Gavin P, Liau, Linda M, Costello, Joseph F, Wick, Wolfgang, Cloughesy, Timothy, Timmer, William C, Wen, Patrick Y, Prins, Robert M, Platten, Michael, and Okada, Hideho

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Vaccine Related, Brain Cancer, Brain Disorders, Orphan Drug, Cancer, Immunization, Rare Diseases, Neurosciences, Good Health and Well Being, Brain Neoplasms, Glioblastoma, Humans, Immunotherapy, Medical Oncology, Neoplasms, Tumor Microenvironment, clinical trial, conference report, glioblastoma, immunosuppression, immunotherapy, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Cancer immunotherapy has made remarkable advances with over 50 separate Food and Drug Administration (FDA) approvals as first- or second-line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T cells, and bispecific T-cell-engaging antibodies. While multiple cancer types now benefit from these immunotherapies, notable exceptions thus far include brain tumors, such as glioblastoma. As such, it seems critical to gain a better understanding of unique mechanistic challenges underlying the resistance of malignant gliomas to immunotherapy, as well as to acquire insights into the development of future strategies. An Immuno-Oncology Think Tank Meeting was held during the 2019 Annual Society for Neuro-Oncology Scientific Conference. Discussants in the fields of neuro-oncology, neurosurgery, neuro-imaging, medical oncology, and cancer immunology participated in the meeting. Sessions focused on topics such as the tumor microenvironment, myeloid cells, T-cell dysfunction, cellular engineering, and translational aspects that are critical and unique challenges inherent with primary brain tumors. In this review, we summarize the discussions and the key messages from the meeting, which may potentially serve as a basis for advancing the field of immune neuro-oncology in a collaborative manner.

Published
2021

6. Elimination of oncogenic KRAS in genetic mouse models eradicates pancreatic cancer by inducing FAS-dependent apoptosis by CD8+ T cells

Author

Mahadevan, Krishnan K., LeBleu, Valerie S., Ramirez, Elena V., Chen, Yang, Li, Bingrui, Sockwell, Amari M., Gagea, Mihai, Sugimoto, Hikaru, Sthanam, Lakshmi Kavitha, Tampe, Desiree, Zeisberg, Michael, Ying, Haoqiang, Jain, Abhinav K., DePinho, Ronald A., Maitra, Anirban, McAndrews, Kathleen M., and Kalluri, Raghu

Published
2023
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7. Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1/CXCR2 results in antitumor immunity and durable response in pancreatic cancer

Author

Gulhati, Pat, Schalck, Aislyn, Jiang, Shan, Shang, Xiaoying, Wu, Chang-Jiun, Hou, Pingping, Ruiz, Sharia Hernandez, Soto, Luisa Solis, Parra, Edwin, Ying, Haoqiang, Han, Jincheng, Dey, Prasenjit, Li, Jun, Deng, Pingna, Sei, Emi, Maeda, Dean Y., Zebala, John A., Spring, Denise J., Kim, Michael, Wang, Huamin, Maitra, Anirban, Moore, Dirk, Clise-Dwyer, Karen, Wang, Y. Alan, Navin, Nicholas E., and DePinho, Ronald A.

Published
2023
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10. Telomere dysfunction instigates inflammation in inflammatory bowel disease

Author

Chakravarti, Deepavali, Lee, Rumi, Multani, Asha S., Santoni, Andrea, Keith, Zachery, Hsu, Wen-Hao, Change, Kyle, Reyes, Laura, Rashid, Asif, Wu, Chang-Jiun, Li, Jun, Zhang, Jiexin, Shim, Hong Seok, Chandra, Krishna, Deng, Pingna, Spring, Denise J., Nielsen, Ole Haagen, Riis, Lene Buhl, Mayigegowda, Kavya Kelagere, Blutt, Sarah E., Zhang, Jianhua, Younes, Mamoun, DuPont, Andrew, Thirumurthi, Selvi, Vilar, Eduardo, Estes, Mary K., Colla, Simona, Shroyer, Noah F., and DePinho, Ronald A.

Published
2021

12. Future cancer research priorities in the USA: a Lancet Oncology Commission

Author

Jaffee, Elizabeth M, Van Dang, Chi, Agus, David B, Alexander, Brian M, Anderson, Kenneth C, Ashworth, Alan, Barker, Anna D, Bastani, Roshan, Bhatia, Sangeeta, Bluestone, Jeffrey A, Brawley, Otis, Butte, Atul J, Coit, Daniel G, Davidson, Nancy E, Davis, Mark, DePinho, Ronald A, Diasio, Robert B, Draetta, Giulio, Frazier, A Lindsay, Futreal, Andrew, Gambhir, Sam S, Ganz, Patricia A, Garraway, Levi, Gerson, Stanton, Gupta, Sumit, Heath, James, Hoffman, Ruth I, Hudis, Cliff, Hughes-Halbert, Chanita, Ibrahim, Ramy, Jadvar, Hossein, Kavanagh, Brian, Kittles, Rick, Le, Quynh-Thu, Lippman, Scott M, Mankoff, David, Mardis, Elaine R, Mayer, Deborah K, McMasters, Kelly, Meropol, Neal J, Mitchell, Beverly, Naredi, Peter, Ornish, Dean, Pawlik, Timothy M, Peppercorn, Jeffrey, Pomper, Martin G, Raghavan, Derek, Ritchie, Christine, Schwarz, Sally W, Sullivan, Richard, Wahl, Richard, Wolchok, Jedd D, Wong, Sandra L, and Yung, Alfred

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Cancer, Rare Diseases, Clinical Research, Good Health and Well Being, Biomedical Research, Forecasting, Health Planning, Health Priorities, Humans, Medical Oncology, National Cancer Institute (U.S.), Neoplasms, Precision Medicine, United States, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.

Published
2017

13. Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

Author

Wang, Qianghu, Hu, Baoli, Hu, Xin, Kim, Hoon, Squatrito, Massimo, Scarpace, Lisa, deCarvalho, Ana C, Lyu, Sali, Li, Pengping, Li, Yan, Barthel, Floris, Cho, Hee Jin, Lin, Yu-Hsi, Satani, Nikunj, Martinez-Ledesma, Emmanuel, Zheng, Siyuan, Chang, Edward, Sauvé, Charles-Etienne Gabriel, Olar, Adriana, Lan, Zheng D, Finocchiaro, Gaetano, Phillips, Joanna J, Berger, Mitchel S, Gabrusiewicz, Konrad R, Wang, Guocan, Eskilsson, Eskil, Hu, Jian, Mikkelsen, Tom, DePinho, Ronald A, Muller, Florian, Heimberger, Amy B, Sulman, Erik P, Nam, Do-Hyun, and Verhaak, Roel GW

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Genetics, Brain Cancer, Neurosciences, Brain Disorders, Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma, Humans, Phenotype, Recurrence, Survival Analysis, T-Lymphocytes, Tumor Microenvironment, disease recurrence, glioblastoma, immune cells, macrophages/microglia, mesenchymal subtype, proneural to mesenchymal transition, tumor evolution, tumor microenvironment, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ T cell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.

Published
2017

14. Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer

Author

Dey, Prasenjit, Baddour, Joelle, Muller, Florian, Wu, Chia Chin, Wang, Huamin, Liao, Wen-Ting, Lan, Zangdao, Chen, Alina, Gutschner, Tony, Kang, Yaan, Fleming, Jason, Satani, Nikunj, Zhao, Di, Achreja, Abhinav, Yang, Lifeng, Lee, Jiyoon, Chang, Edward, Genovese, Giannicola, Viale, Andrea, Ying, Haoqiang, Draetta, Giulio, Maitra, Anirban, Wang, Y Alan, Nagrath, Deepak, and DePinho, Ronald A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Rare Diseases, Cancer, Pancreatic Cancer, Digestive Diseases, Biotechnology, Ovarian Cancer, Development of treatments and therapeutic interventions, Aetiology, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, AMP-Activated Protein Kinases, Amino Acids, Branched-Chain, Animals, Biocatalysis, Carcinoma, Pancreatic Ductal, Gene Deletion, Humans, Ketoglutaric Acids, Malate Dehydrogenase, Male, Mice, Minor Histocompatibility Antigens, Mitochondria, NADP, Pancreatic Neoplasms, Pregnancy Proteins, Reactive Oxygen Species, Sterol Regulatory Element Binding Protein 1, Transaminases, General Science & Technology
Abstract

The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis. Here we show that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP activated protein kinase (AMPK), which in turn directly suppresses sterol regulatory element-binding protein 1 (SREBP1)-directed transcription of its direct targets including the BCAT2 branched-chain amino acid transaminase 2) gene. BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to α-ketoglutarate (α-KG) thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with this intractable disease.

Published
2017

15. 3D imaging analysis on an organoid-based platform guides personalized treatment in pancreatic ductal adenocarcinoma

Author

Kang, Ya'an, Deng, Jenying, Ling, Jianhua, Li, Xinqun, Chiang, Yi-Ju, Koay, Eugene J., Wang, Huamin, Burks, Jared K., Chiao, Paul J., Hurd, Mark W., Bhutani, Manoop S., Lee, Jeffrey H., Weston, Brian R., Maitra, Anirban, Ikoma, Naruhiko, Tzeng, Ching-Wei D., Lee, Jeffrey E., DePinho, Ronald A., Wolff, Robert A., Pant, Shubham, McAllister, Florencia, Katz, Matthew H.G., Fleming, Jason B., and Kim, Michael P.

Subjects
Oncology, Experimental, Cancer -- Research, Pancreatic cancer -- Diagnosis -- Drug therapy, Health care industry
Abstract

BACKGROUND. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient- derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy. METHODS. We retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, [alpha]-smooth muscle actin ([alpha]-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test. RESULTS. Immunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA199 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P < 0.0001). [alpha]-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046). CONCLUSION. Heterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of- care chemotherapy. Ratios of [alpha]-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC. FUNDING. NIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672)., Introduction Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide. In the United States, researchers estimated 60,430 new PDAC cases and 48,220 PDAC-related deaths in 2021 alone. [...]

Published
2022
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17. Abstract B082: Extinction of oncogenic Kras in genetic mouse models eradicates pancreatic cancer by inducing Fas-dependent apoptosis by CD8+ T cells

Author

LeBleu, Valerie S., primary, Mahadevan, Krishnan K., additional, Ramirez, Elena V., additional, Chen, Yang, additional, Li, Bingrui, additional, Sockwell, Amari M., additional, Gagea, Mihai, additional, Sugimoto, Hikaru, additional, Tampe, Desiree, additional, Zeisberg, Michael, additional, Ying, Haoqiang, additional, Jain, Abhinav K., additional, DePinho, Ronald A., additional, Maitra, Aniban, additional, McAndrews, Kathleen M., additional, and Kalluri, Raghu, additional

Published
2024
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20. Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth

Author

Hu, Baoli, Wang, Qianghu, Wang, Y Alan, Hua, Sujun, Sauvé, Charles-Etienne Gabriel, Ong, Derrick, Lan, Zheng D, Chang, Qing, Ho, Yan Wing, Monasterio, Marta Moreno, Lu, Xin, Zhong, Yi, Zhang, Jianhua, Deng, Pingna, Tan, Zhi, Wang, Guocan, Liao, Wen-Ting, Corley, Lynda J, Yan, Haiyan, Zhang, Junxia, You, Yongping, Liu, Ning, Cai, Linbo, Finocchiaro, Gaetano, Phillips, Joanna J, Berger, Mitchel S, Spring, Denise J, Hu, Jian, Sulman, Erik P, Fuller, Gregory N, Chin, Lynda, Verhaak, Roeland GW, and DePinho, Ronald A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Neurosciences, Cancer, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Nonembryonic - Human, Rare Diseases, Genetics, Brain Cancer, Brain Disorders, Stem Cell Research, Endothelial Cells, Epigenomics, Gene Expression Regulation, Neoplastic, Glioblastoma, Homeodomain Proteins, Humans, Neoplasm Invasiveness, Neural Stem Cells, PAX6 Transcription Factor, Proto-Oncogene Proteins c-akt, Transcription Factors, Wnt-5a Protein, cancer stem cell differentiation, glioblastoma, recurrence, tumor microenvironment, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.

Published
2016

21. Data from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression

Author

Hsu, Wen-Hao, primary, LaBella, Kyle A., primary, Lin, Yiyun, primary, Xu, Ping, primary, Lee, Rumi, primary, Hsieh, Cheng-En, primary, Yang, Lei, primary, Zhou, Ashley, primary, Blecher, Jonathan M., primary, Wu, Chang-Jiun, primary, Lin, Kangyu, primary, Shang, Xiaoying, primary, Jiang, Shan, primary, Spring, Denise J., primary, Xia, Yan, primary, Chen, Peiwen, primary, Shen, John Paul, primary, Kopetz, Scott, primary, and DePinho, Ronald A., primary

Published
2023
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22. Supplementary Figure S7 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression

Author

Hsu, Wen-Hao, primary, LaBella, Kyle A., primary, Lin, Yiyun, primary, Xu, Ping, primary, Lee, Rumi, primary, Hsieh, Cheng-En, primary, Yang, Lei, primary, Zhou, Ashley, primary, Blecher, Jonathan M., primary, Wu, Chang-Jiun, primary, Lin, Kangyu, primary, Shang, Xiaoying, primary, Jiang, Shan, primary, Spring, Denise J., primary, Xia, Yan, primary, Chen, Peiwen, primary, Shen, John Paul, primary, Kopetz, Scott, primary, and DePinho, Ronald A., primary

Published
2023
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23. Supplementary Table S5 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression

Author

Hsu, Wen-Hao, primary, LaBella, Kyle A., primary, Lin, Yiyun, primary, Xu, Ping, primary, Lee, Rumi, primary, Hsieh, Cheng-En, primary, Yang, Lei, primary, Zhou, Ashley, primary, Blecher, Jonathan M., primary, Wu, Chang-Jiun, primary, Lin, Kangyu, primary, Shang, Xiaoying, primary, Jiang, Shan, primary, Spring, Denise J., primary, Xia, Yan, primary, Chen, Peiwen, primary, Shen, John Paul, primary, Kopetz, Scott, primary, and DePinho, Ronald A., primary

Published
2023
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24. An enolase inhibitor for the targeted treatment of ENO1-deleted cancers

Author

Lin, Yu-Hsi, Satani, Nikunj, Hammoudi, Naima, Yan, Victoria C., Barekatain, Yasaman, Khadka, Sunada, Ackroyd, Jeffrey J., Georgiou, Dimitra K., Pham, Cong-Dat, Arthur, Kenisha, Maxwell, David, Peng, Zhenghong, Leonard, Paul G., Czako, Barbara, Pisaneschi, Federica, Mandal, Pijus, Sun, Yuting, Zielinski, Rafal, Pando, Susana Castro, Wang, Xiaobo, Tran, Theresa, Xu, Quanyu, Wu, Qi, Jiang, Yongying, Kang, Zhijun, Asara, John M., Priebe, Waldemar, Bornmann, William, Marszalek, Joseph R., DePinho, Ronald A., and Muller, Florian L.

Published
2020
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27. Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.

Author

Zheng, Xingnan, Zhai, Bo, Koivunen, Peppi, Shin, Sandra, Lu, Gang, Liu, Jiayun, Geisen, Christoph, Chakraborty, Abhishek, Moslehi, Javid, Smalley, David, Wei, Xin, Chen, Xian, Chen, Zhengming, Beres, Justine, Zhang, Jing, Tsao, Jen, Brenner, Mitchell, Zhang, Yuqing, Fan, Cheng, DePinho, Ronald, Paik, Jihye, Gygi, Steven, Kaelin, William, and Zhang, Qing

Subjects
Cyclin D1, EglN2, FOXO3a, USP9x, breast cancer, prolyl hydroxylation, Animals, Cell Line, Cells, Cultured, Cyclin D1, Forkhead Box Protein O3, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Hydroxylation, Hypoxia-Inducible Factor-Proline Dioxygenases, MCF-7 Cells, Mice, Protein Binding, Protein Stability, Ubiquitin Thiolesterase
Abstract

The three EglN prolyl hydroxylases (EglN1, EglN2, and EglN3) regulate the stability of the HIF transcription factor. We recently showed that loss of EglN2, however, also leads to down-regulation of Cyclin D1 and decreased cell proliferation in a HIF-independent manner. Here we report that EglN2 can hydroxylate FOXO3a on two specific prolyl residues in vitro and in vivo. Hydroxylation of these sites prevents the binding of USP9x deubiquitinase, thereby promoting the proteasomal degradation of FOXO3a. FOXO transcription factors can repress Cyclin D1 transcription. Failure to hydroxylate FOXO3a promotes its accumulation in cells, which in turn suppresses Cyclin D1 expression. These findings provide new insights into post-transcriptional control of FOXO3a and provide a new avenue for pharmacologically altering Cyclin D1 activity.

Published
2014

29. Oncogenic KRAS drives lipo-fibrogenesis to promote angiogenesis and colon cancer progression

Author

Hsu, Wen-Hao, primary, LaBella, Kyle A., additional, Lin, Yiyun, additional, Xu, Ping, additional, Lee, Rumi, additional, Hsieh, Cheng-En, additional, Yang, Lei, additional, Zhou, Ashley, additional, Blecher, Jonathan M., additional, Wu, Chang-Jiun, additional, Lin, Kangyu, additional, Shang, Xiaoying, additional, Jiang, Shan, additional, Spring, Denise J., additional, Xia, Yan, additional, Chen, Peiwen, additional, Shen, John Paul., additional, Kopetz, Scott, additional, and DePinho, Ronald A., additional

Published
2023
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30. KRAS inhibition activates an actionable CD24 ‘don’t eat me’ signal in pancreas cancer

Author

Wei, Yongkun, primary, Liu, Minghui, additional, Yen, Er-Yen, additional, Yao, Jun, additional, Nguyen, Phuoc T, additional, Wang, Xiaofei, additional, Yang, Zecheng, additional, Yousef, Abdelrahman, additional, Pan, Dean, additional, Jin, Yanqing, additional, Theady, Madelaine S., additional, Park, Jungho, additional, Cai, Yiming, additional, Takeda, Mitsunobu, additional, Vasquez, Matthew, additional, Zhou, Yong, additional, Zhao, Hong, additional, Viale, Andrea, additional, Wang, Huamin, additional, Zhao, Dan, additional, DePinho, Ronald A., additional, Yao, Wantong, additional, and Ying, Haoqiang, additional

Published
2023
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32. Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer

Author

Yao, Wantong, Rose, Johnathon L., Wang, Wei, Seth, Sahil, Jiang, Hong, Taguchi, Ayumu, Liu, Jintan, Yan, Liang, Kapoor, Avnish, Hou, Pingping, Chen, Ziheng, Wang, Qiuyun, Nezi, Luigi, Xu, Zhaohui, Yao, Jun, Hu, Baoli, Pettazzoni, Piergiorgio F., Ho, I Lin, Feng, Ningping, Ramamoorthy, Vandhana, Jiang, Shan, Deng, Pingna, Ma, Grace J., Den, Peter, Tan, Zhi, Zhang, Shu Xing, Wang, Huamin, Wang, Y. Alan, Deem, Angela K., Fleming, Jason B., Carugo, Alessandro, Heffernan, Timothy P., Maitra, Anirban, Viale, Andrea, Ying, Haoqiang, Hanash, Samir, DePinho, Ronald A., and Draetta, Giulio F.

Published
2019
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35. High-Resolution Genomic Profiles of Human Lung Cancer

Author

Tonon, Giovanni, Wong, Kwok-Kin, Maulik, Gautam, Brennan, Cameron, Feng, Bin, Zhang, Yunyu, Khatry, Deepak B., Protopopov, Alexei, You, Mingjian James, Aguirre, Andrew J., Martin, Eric S., Yang, Zhaohui, Ji, Hongbin, Chin, Lynda, DePinho, Ronald A., and Cavenee, Webster K.

Published
2005

38. Impact papers on aging in 2009

Author

Blagosklonny, Mikhail V, Campisi, Judy, Sinclair, David A, Bartke, Andrzej, Blasco, Maria A, Bonner, William M, Bohr, Vilhelm A, Jr, Robert M Brosh, Brunet, Anne, DePinho, Ronald A, Donehower, Lawrence A, Finch, Caleb E, Finkel, Toren, Gorospe, Myriam, Gudkov, Andrei V, Hall, Michael N, Hekimi, Siegfried, Helfand, Stephen L, Karlseder, Jan, Kenyon, Cynthia, Kroemer, Guido, Longo, Valter, Nussenzweig, Andre, Osiewacz, Heinz D, Peeper, Daniel S, Rando, Thomas A, Rudolph, K Lenhard, Sassone-Corsi, Paolo, Serrano, Manuel, Sharpless, Norman E, Skulachev, Vladimir P, Tilly, Jonathan L, Tower, John, Verdin, Eric, and Vijg, Jan

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Aging, 1.1 Normal biological development and functioning, Underpinning research, Good Health and Well Being, Adult Stem Cells, Animals, Autophagy, Caloric Restriction, Cellular Reprogramming, Circadian Rhythm, DNA Damage, Humans, Mitochondria, Neoplasms, Oxidative Stress, RNA Processing, Post-Transcriptional, Telomere, aging, senescence, signal transduction, genes for longevity, Biochemistry and cell biology, Clinical sciences
Abstract

The Editorial Board of Aging reviews research papers published in 2009, which they believe have or will have significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacological interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically.

Published
2010

39. High-Resolution Characterization of the Pancreatic Adenocarcinoma Genome

Author

Aguirre, Andrew J., Brennan, Cameron, Bailey, Gerald, Sinha, Raktim, Feng, Bin, Leo, Christopher, Zhang, Yunyu, Zhang, Jean, Gans, Joseph D., Bardeesy, Nabeel, Cauwels, Craig, Cordon-Cardo, Carlos, Redston, Mark S., DePinho, Ronald A., Chin, Lynda, and Cantley, Lewis C.

Published
2004

42. PAF promotes stemness and radioresistance of glioma stem cells

Author

Ong, Derrick Sek Tong, Hu, Baoli, Ho, Yan Wing, Sauvé, Charles-Etienne Gabriel, Bristow, Christopher A., Wang, Qianghu, Multani, Asha S., Chen, Peiwen, Nezi, Luigi, Jiang, Shan, Gorman, Claire Elizabeth, Monasterio, Marta Moreno, Koul, Dimpy, Marchesini, Matteo, Colla, Simona, Jin, Eun-Jung, Sulman, Erik P., Spring, Denise J., Yung, Wai-Kwan Alfred, Verhaak, Roel G. W., Chin, Lynda, Wang, Y. Alan, and DePinho, Ronald A.

Published
2017

43. BrafV600E cooperates with Pten loss to induce metastatic melanoma

Author

Dankort, David, Curley, David P, Cartlidge, Robert A, Nelson, Betsy, Karnezis, Anthony N, Damsky Jr, William E, You, Mingjian J, DePinho, Ronald A, McMahon, Martin, and Bosenberg, Marcus

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Cancer, Alleles, Animals, Cell Line, Tumor, Cell Proliferation, Mechanistic Target of Rapamycin Complex 1, Melanoma, Mice, Mice, Transgenic, Multiprotein Complexes, Neoplasm Metastasis, PTEN Phosphohydrolase, Proteins, Proto-Oncogene Proteins B-raf, TOR Serine-Threonine Kinases, Transcription Factors, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Mutational activation of BRAF is the earliest and most common genetic alteration in human melanoma. To build a model of human melanoma, we generated mice with conditional melanocyte-specific expression of BRaf(V600E). Upon induction of BRaf(V600E) expression, mice developed benign melanocytic hyperplasias that failed to progress to melanoma over 15-20 months. By contrast, expression of BRaf(V600E) combined with Pten tumor suppressor gene silencing elicited development of melanoma with 100% penetrance, short latency and with metastases observed in lymph nodes and lungs. Melanoma was prevented by inhibitors of mTorc1 (rapamycin) or MEK1/2 (PD325901) but, upon cessation of drug administration, mice developed melanoma, indicating the presence of long-lived melanoma-initiating cells in this system. Notably, combined treatment with rapamycin and PD325901 led to shrinkage of established melanomas. These mice, engineered with a common genetic profile to human melanoma, provide a system to study melanoma's cardinal feature of metastasis and for preclinical evaluation of agents designed to prevent or treat metastatic disease.

Published
2009

48. Telomere dysfunction activates YAP1 to drive tissue inflammation

Author

Chakravarti, Deepavali, Hu, Baoli, Mao, Xizeng, Rashid, Asif, Li, Jiexi, Li, Jun, Liao, Wen-ting, Whitley, Elizabeth M., Dey, Prasenjit, Hou, Pingping, LaBella, Kyle A., Chang, Andrew, Wang, Guocan, Spring, Denise J., Deng, Pingna, Zhao, Di, Liang, Xin, Lan, Zhengdao, Lin, Yiyun, Sarkar, Sharmistha, Terranova, Christopher, Deribe, Yonathan Lissanu, Blutt, Sarah E., Okhuysen, Pablo, Zhang, Jianhua, Vilar, Eduardo, Nielsen, Ole Haagen, Dupont, Andrew, Younes, Mamoun, Patel, Kalyani R., Shroyer, Noah F., Rai, Kunal, Estes, Mary K., Wang, Y. Alan, Bertuch, Alison A., and DePinho, Ronald A.

Published
2020
Full Text
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50. p19ARF Targets Certain E2F Species for Degradation

Author

Martelli, Fabio, Hamilton, Timothy, Silver, Daniel P., Sharpless, Norman E., Bardeesy, Nabeel, Rokas, Mihail, DePinho, Ronald A., Livingston, David M., and Grossman, Steven R.

Published
2001

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