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Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey
Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey
Department of Cancer Biology Faculty Papers
The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor …
Sighting Acute Myocardial Infarction Through Platelet Gene Expression., Giuliana Gobbi, Cecilia Carubbi, Guidantonio Malagoli Tagliazucchi, Elena Masselli, Prisco Mirandola, Filippo Pigazzani, Antonio Crocamo, Maria Francesca Notarangelo, Sergio Suma, Elvezia Paraboschi, Giuseppe Maglietta, Srikanth Nagalla, Giulia Pozzi, Daniela Galli, Mauro Vaccarezza, Paolo Fortina, Sankar Addya, Adam Ertel, Paul Bray, Stefano Duga, Carlo Berzuini, Marco Vitale, Diego Ardissino
Sighting Acute Myocardial Infarction Through Platelet Gene Expression., Giuliana Gobbi, Cecilia Carubbi, Guidantonio Malagoli Tagliazucchi, Elena Masselli, Prisco Mirandola, Filippo Pigazzani, Antonio Crocamo, Maria Francesca Notarangelo, Sergio Suma, Elvezia Paraboschi, Giuseppe Maglietta, Srikanth Nagalla, Giulia Pozzi, Daniela Galli, Mauro Vaccarezza, Paolo Fortina, Sankar Addya, Adam Ertel, Paul Bray, Stefano Duga, Carlo Berzuini, Marco Vitale, Diego Ardissino
Department of Cancer Biology Faculty Papers
Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression …
Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl
Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl
Department of Cancer Biology Faculty Papers
The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X …
Identification Of Monocyte-Like Precursors Of Granulocytes In Cancer As A Mechanism For Accumulation Of Pmn-Mdscs., Jérôme Mastio, Thomas Condamine, George Dominguez, Andrew V Kossenkov, Laxminarasimha Donthireddy, Filippo Veglia, Cindy Lin, Fang Wang, Shuyu Fu, Jie Zhou, Patrick Viatour, Sergio Lavilla-Alonso, Alexander T. Polo, Evgenii N. Tcyganov, Charles Mulligan, Brian Nam, Joseph Bennett, Gregory Masters, Michael Guarino, Amit Kumar, Yulia Nefedova, Robert H. Vonderheide, Lucia R. Languino, Scott I. Abrams, Dmitry I. Gabrilovich
Identification Of Monocyte-Like Precursors Of Granulocytes In Cancer As A Mechanism For Accumulation Of Pmn-Mdscs., Jérôme Mastio, Thomas Condamine, George Dominguez, Andrew V Kossenkov, Laxminarasimha Donthireddy, Filippo Veglia, Cindy Lin, Fang Wang, Shuyu Fu, Jie Zhou, Patrick Viatour, Sergio Lavilla-Alonso, Alexander T. Polo, Evgenii N. Tcyganov, Charles Mulligan, Brian Nam, Joseph Bennett, Gregory Masters, Michael Guarino, Amit Kumar, Yulia Nefedova, Robert H. Vonderheide, Lucia R. Languino, Scott I. Abrams, Dmitry I. Gabrilovich
Department of Cancer Biology Faculty Papers
We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be …
The Bone Extracellular Matrix As An Ideal Milieu For Cancer Cell Metastases., Alexus D. Kolb, Karen M. Bussard
The Bone Extracellular Matrix As An Ideal Milieu For Cancer Cell Metastases., Alexus D. Kolb, Karen M. Bussard
Department of Cancer Biology Faculty Papers
Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to …
Myc-Mediated Transcriptional Regulation Of The Mitochondrial Chaperone Trap1 Controls Primary And Metastatic Tumor Growth., Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Jagadish C. Ghosh, Andrew V Kossenkov, Hsin-Yao Tang, Shiv Ram Krishn, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri
Myc-Mediated Transcriptional Regulation Of The Mitochondrial Chaperone Trap1 Controls Primary And Metastatic Tumor Growth., Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Jagadish C. Ghosh, Andrew V Kossenkov, Hsin-Yao Tang, Shiv Ram Krishn, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri
Department of Cancer Biology Faculty Papers
The role of mitochondria in cancer continues to be debated, and whether exploitation of mitochondrial functions is a general hallmark of malignancy or a tumor- or context-specific response is still unknown. Using a variety of cancer cell lines and several technical approaches, including siRNA-mediated gene silencing, ChIP assays, global metabolomics and focused metabolite analyses, bioenergetics, and cell viability assays, we show that two oncogenic Myc proteins, c-Myc and N-Myc, transcriptionally control the expression of the mitochondrial chaperone TNFR-associated protein- 1 (TRAP1) in cancer. In turn, this Myc-mediated regulation preserved the folding and function of mitochondrial oxidative phosphorylation (OXPHOS) complex II …
M6a Mrna Demethylase Fto Regulates Melanoma Tumorigenicity And Response To Anti-Pd-1 Blockade, Seungwon Yang, Jiangbo Wei, Yan-Hong Cui, Gayoung Park, Palak Shah, Yu Deng, Andrew E. Aplin, Zhike Lu, Seungmin Hwang, Chuan He, Yu-Ying He
M6a Mrna Demethylase Fto Regulates Melanoma Tumorigenicity And Response To Anti-Pd-1 Blockade, Seungwon Yang, Jiangbo Wei, Yan-Hong Cui, Gayoung Park, Palak Shah, Yu Deng, Andrew E. Aplin, Zhike Lu, Seungmin Hwang, Chuan He, Yu-Ying He
Department of Cancer Biology Faculty Papers
Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of …
Tumor-Derived Extracellular Vesicles Require Β1 Integrins To Promote Anchorage-Independent Growth., Rachel M. Derita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter Mccue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino
Tumor-Derived Extracellular Vesicles Require Β1 Integrins To Promote Anchorage-Independent Growth., Rachel M. Derita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter Mccue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino
Department of Cancer Biology Faculty Papers
The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation …
Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard
Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard
Department of Cancer Biology Faculty Papers
INTRODUCTION: In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are …
Cyclin D1 Integrates G9a-Mediated Histone Methylation., Zhiping Li, Xuanmao Jiao, Gabriele Di Sante, Adam Ertel, Mathew C. Casimiro, Min Wang, Sanjay Katiyar, Xiaoming Ju, D. V. Klopfenstein, Aydin Tozeren, William Dampier, Iouri Chepelev, Albert Jeltsch, Richard G. Pestell
Cyclin D1 Integrates G9a-Mediated Histone Methylation., Zhiping Li, Xuanmao Jiao, Gabriele Di Sante, Adam Ertel, Mathew C. Casimiro, Min Wang, Sanjay Katiyar, Xiaoming Ju, D. V. Klopfenstein, Aydin Tozeren, William Dampier, Iouri Chepelev, Albert Jeltsch, Richard G. Pestell
Department of Cancer Biology Faculty Papers
Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing cell-cycle …