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Full-Text Articles in Medicine and Health Sciences
Myc Regulates Ribosome Biogenesis And Mitochondrial Gene Expression Programs Through Its Interaction With Host Cell Factor-1., Tessa M. Popay, Jing Wang, Clare M. Adams, Gregory Caleb Howard, Simona G. Codreanu, Stacy D. Sherrod, John A. Mclean, Lance R. Thomas, Shelly L. Lorey, Yuichi J. Machida, April M. Weissmiller, Christine M. Eischen, Qi Liu, William P. Tansey
Myc Regulates Ribosome Biogenesis And Mitochondrial Gene Expression Programs Through Its Interaction With Host Cell Factor-1., Tessa M. Popay, Jing Wang, Clare M. Adams, Gregory Caleb Howard, Simona G. Codreanu, Stacy D. Sherrod, John A. Mclean, Lance R. Thomas, Shelly L. Lorey, Yuichi J. Machida, April M. Weissmiller, Christine M. Eischen, Qi Liu, William P. Tansey
Department of Cancer Biology Faculty Papers
The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global …
Cadm1 Is A Twist1-Regulated Suppressor Of Invasion And Survival., Edward J. Hartsough, Michele B. Weiss, Shea A. Heilman, Timothy J. Purwin, Curtis H Kugel, Sheera R. Rosenbaum, Dan A. Erkes, Manoela Tiago, Kim Hookim, Inna Chervoneva, Andrew E. Aplin
Cadm1 Is A Twist1-Regulated Suppressor Of Invasion And Survival., Edward J. Hartsough, Michele B. Weiss, Shea A. Heilman, Timothy J. Purwin, Curtis H Kugel, Sheera R. Rosenbaum, Dan A. Erkes, Manoela Tiago, Kim Hookim, Inna Chervoneva, Andrew E. Aplin
Department of Cancer Biology Faculty Papers
Metastatic cancer remains a clinical challenge; however, patients diagnosed prior to metastatic dissemination have a good prognosis. The transcription factor, TWIST1 has been implicated in enhancing the migration and invasion steps within the metastatic cascade, but the range of TWIST1-regulated targets is poorly described. In this study, we performed expression profiling to identify the TWIST1-regulated transcriptome of melanoma cells. Gene ontology pathway analysis revealed that TWIST1 and epithelial to mesenchymal transition (EMT) were inversely correlated with levels of cell adhesion molecule 1 (CADM1). Chromatin immunoprecipitation (ChIP) studies and promoter assays demonstrated that TWIST1 physically interacts with the CADM1 promoter, suggesting …
Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta
Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta
Department of Cancer Biology Faculty Papers
Philadelphia chromosome–positive acute lymphoblastic leukemia (Phþ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Phþ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Phþ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced …
Erk-Mediated Phosphorylation Regulates Sox10 Sumoylation And Targets Expression In Mutant Braf Melanoma., Shujun Han, Yibo Ren, Wangxiao He, Huadong Liu, Zhe Zhi, Xinliang Zhu, Tielin Yang, Yu Rong, Bohan Ma, Timothy J. Purwin, Zhenlin Ouyang, Caixia Li, Xun Wang, Xueqiang Wang, Huizi Yang, Yan Zheng, Andrew E. Aplin, Jiankang Liu, Yongping Shao
Erk-Mediated Phosphorylation Regulates Sox10 Sumoylation And Targets Expression In Mutant Braf Melanoma., Shujun Han, Yibo Ren, Wangxiao He, Huadong Liu, Zhe Zhi, Xinliang Zhu, Tielin Yang, Yu Rong, Bohan Ma, Timothy J. Purwin, Zhenlin Ouyang, Caixia Li, Xun Wang, Xueqiang Wang, Huizi Yang, Yan Zheng, Andrew E. Aplin, Jiankang Liu, Yongping Shao
Department of Cancer Biology Faculty Papers
In human mutant BRAF melanoma cells, the stemness transcription factor FOXD3 is rapidly induced by inhibition of ERK1/2 signaling and mediates adaptive resistance to RAF inhibitors. However, the mechanism underlying ERK signaling control of FOXD3 expression remains unknown. Here we show that SOX10 is both necessary and sufficient for RAF inhibitor-induced expression of FOXD3 in mutant BRAF melanoma cells. SOX10 activates the transcription of FOXD3 by binding to a regulatory element in FOXD3 promoter. Phosphorylation of SOX10 by ERK inhibits its transcription activity toward multiple target genes by interfering with the sumoylation of SOX10 at K55, which is essential for …
Response And Resistance To Paradox-Breaking Braf Inhibitor In Melanomas, Edward J. Hartsough, Curtis H. Kugel, Michael J. Vido, Adam C. Berger, Timothy J. Purwin, Allison F. Goldberg, Michael A. Davies, Matthew J. Schiewer, Karen E. Knudsen, Gideon Bollag, Andrew E. Aplin
Response And Resistance To Paradox-Breaking Braf Inhibitor In Melanomas, Edward J. Hartsough, Curtis H. Kugel, Michael J. Vido, Adam C. Berger, Timothy J. Purwin, Allison F. Goldberg, Michael A. Davies, Matthew J. Schiewer, Karen E. Knudsen, Gideon Bollag, Andrew E. Aplin
Department of Cancer Biology Faculty Papers
FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was …
Decoding Critical Long Non-Coding Rna In Ovarian Cancer Epithelial-To-Mesenchymal Transition., Ramkrishna Mitra, Xi Chen, Evan J. Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M. Eischen
Decoding Critical Long Non-Coding Rna In Ovarian Cancer Epithelial-To-Mesenchymal Transition., Ramkrishna Mitra, Xi Chen, Evan J. Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M. Eischen
Department of Cancer Biology Faculty Papers
Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in …
Hormone Whodunit: Clues For Solving The Case Of Intratumor Androgen Production., Karen E Knudsen
Hormone Whodunit: Clues For Solving The Case Of Intratumor Androgen Production., Karen E Knudsen
Department of Cancer Biology Faculty Papers
One of the key mechanisms by which prostate cancer cells evade hormone therapy is through intratumor testosterone production. New evidence points toward androstenedione as a potential precursor of intratumor androgen production and furthers nomination of AKR1C3 as a therapeutic target in advanced disease. Clin Cancer Res; 20(21); 5343-5. ©2014 AACR.
Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell
Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell
Department of Cancer Biology Faculty Papers
The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …
Small Non-Coding Rnas Govern Mammary Gland Tumorigenesis., Zuoren Yu, Richard Pestell
Small Non-Coding Rnas Govern Mammary Gland Tumorigenesis., Zuoren Yu, Richard Pestell
Department of Cancer Biology Faculty Papers
Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of miRNAs in the regulation of mammary gland tumorigenesis has been widely studied while the role for other small non-coding RNAs remains unclear. Here we summarize the involvement of miRNA in breast cancer onset and progression through regulating the cell cycle and cellular proliferation. The regulation of breast cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the emerging evidence demonstrating the involvement of piRNA and snoRNA in breast cancer is briefly described.
A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon
A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon
Department of Cancer Biology Faculty Papers
Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent …