1. Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.

    Journal of Hepatology 65(2):325 (2016) PMID 27117591

    Pediatric liver cancer is a rare but serious disease whose incidence is rising, and for which the therapeutic options are limited. Development of more targeted, less toxic therapies is hindered by the lack of an experimental animal model that captures the heterogeneity and metastatic capability ...
  2. Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer.

    Cell Reports 15(7):1493 (2016) PMID 27160903 PMCID PMC4914391

    3q26.2 amplification in high-grade serous ovarian cancer leads to increased expression of mature microRNA miR551b-3p, which is associated with poor clinical outcome. Importantly, miR551b-3p contributes to resistance to apoptosis and increased survival and proliferation of cancer cells in vitro a...
  3. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors.

    Journal of Clinical Investigation 126(5):1834 (2016) PMID 27043285 PMCID PMC4855947

    Targeting multiple components of the MAPK pathway can prolong the survival of patients with BRAFV600E melanoma. This approach is not curative, as some BRAF-mutated melanoma cells are intrinsically resistant to MAPK inhibitors (MAPKi). At the systemic level, our knowledge of how signaling pathway...
  4. HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors.

    Cancer Research 76(9):2720 (2016) PMID 26984758 PMCID PMC4939897

    The stress-inducible chaperone protein HSP70 (HSPA1) is implicated in melanoma development, and HSP70 inhibitors exert tumor-specific cytotoxic activity in cancer. In this study, we documented that a significant proportion of melanoma tumors express high levels of HSP70, particularly at advanced...
  5. Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies.

    Clinical Cancer Research 22(7):1592 (2016) PMID 26673799 PMCID PMC4818716

    To test second-line personalized medicine combination therapies, based on genomic and proteomic data, in patient-derived xenograft (PDX) models. We established 12 PDXs from BRAF inhibitor-progressed melanoma patients. Following expansion, PDXs were analyzed using targeted sequencing and reverse-...
  6. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma.

    Cell Reports 14(10):2476 (2016) PMID 26947078 PMCID PMC4794376

    On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression), we classified 894 renal cell carcinomas (RCCs) of various histologic types into nine major genomic subtypes. Site of origin within the nephron...
  7. MAPK Activation Predicts Poor Outcome and the MEK Inhibitor, Selumetinib, Reverses Antiestrogen Resistance in ER-Positive High-Grade Serous Ovarian Cancer.

    Clinical Cancer Research 22(4):935 (2016) PMID 26482043 PMCID PMC4755805

    Although 67% of high-grade serous ovarian cancers (HGSOC) express the estrogen receptor (ER), most fail antiestrogen therapy. Because MAPK activation is frequent in ovarian cancer, we investigated if estrogen regulates MAPK and if MEK inhibition (MEKi) reverses antiestrogen resistance. Effects o...
  8. Integrative Protein-Based Prognostic Model for Early-Stage Endometrioid Endometrial Cancer.

    Clinical Cancer Research 22(2):513 (2016) PMID 26224872 PMCID PMC4715969

    Endometrioid endometrial carcinoma (EEC) is the major histologic type of endometrial cancer, the most prevalent gynecologic malignancy in the United States. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recur...
  9. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
    W Marston Linehan, Paul T Spellman, Christopher J Ricketts, Chad J Creighton, Suzanne Fei, Caleb Davis, David A Wheeler, Bradley A Murray, Laura Schmidt, Cathy D Vocke, Myron Peto, Abu Amar Al Mamun, Eve Shinbrot, Anurag Sethi, Samira Brooks, W Kimryn Rathmell, Angela N Brooks, Katherine A Hoadley, A Gordon Robertson, Denise Brooks, Reanne Bowlby, Sara Sadeghi, Hui Shen, Daniel J Weisenberger, Moiz Bootwalla, Stephen Baylin, Peter W Laird, Andrew D Cherniack, Gordon Saksena, Scott Haake, Jun Li, Han Liang, Yiling Lu, Gordon B Mills, Rehan Akbani, Mark D Leiserson, Benjamin J Raphael, Pavana Anur, Donald Bottaro, Laurence Albiges, Nandita Barnabas, Toni K Choueiri, Bogdan Czerniak, Andrew K Godwin, Ari Hakimi, Thai Ho, James Hsieh, Michael Ittmann, William Y Kim, Bhavani Krishnan, Maria J Merino, Kenna R Mills Shaw, Victor E Reuter, Ed Reznik, Carl Shelley, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Satish Tickoo, Kenneth Burnett, Daniel Crain, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph D Paulauskis, Robert J Penny, Candace Shelton, W Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Melissa T Avedon, Jay Bowen, Julie M Gastier-Foster, Mark Gerken, Kristen M Leraas, Tara M Lichtenberg, Nilsa C Ramirez, Tracie Santos, Lisa Wise, Erik Zmuda, John A Demchok, Ina Felau, Carolyn M Hutter, Margi Sheth, Heidi J Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C Zenklusen, Jiashan Zhang, Brenda Ayala, Julien Baboud, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Adrian Ally, Miruna Balasundaram, Saianand Balu, Rameen Beroukhim, Tom Bodenheimer, Christian Buhay, Yaron S N Butterfield, Rebecca Carlsen, Scott L Carter, Hsu Chao, Eric Chuah, Amanda Clarke, Kyle R Covington, Mahmoud Dahdouli, Ninad Dewal, Noreen Dhalla, Harsha V Doddapaneni, Jennifer A Drummond, Stacey B Gabriel, Richard A Gibbs, Ranabir Guin, Walker Hale, Alicia Hawes, D Neil Hayes, Robert A Holt, Alan P Hoyle, Stuart R Jefferys, Steven M Jones, Corbin D Jones, Divya Kalra, Christie Kovar, Lora Lewis, Jie Li, Yussanne Ma, Marco A Marra, Michael Mayo, Shaowu Meng, Matthew Meyerson, Piotr A Mieczkowski, Richard A Moore, Donna Morton, Lisle E Mose, Andrew J Mungall, Donna Muzny, Joel S Parker, Charles M Perou, Jeffrey Roach, Jacqueline E Schein, Steven E Schumacher, Yan Shi, Janae V Simons, Payal Sipahimalani, Tara Skelly, Matthew G Soloway, Carrie Sougnez, Angela Tam, Donghui Tan, Nina Thiessen, Umadevi Veluvolu, Min Wang, Matthew D Wilkerson, Tina Wong, Junyuan Wu, Liu Xi, Jane Zhou, Jason Bedford, Fengju Chen, Yao Fu, Mark Gerstein, David Haussler, Katayoon Kasaian, Phillip Lai, Shiyun Ling, Amie Radenbaugh, David Van Den Berg, John N Weinstein, Jingchun Zhu, Monique Albert, Iakovina Alexopoulou, Jeremiah Andersen, J Todd Auman, John Bartlett, Sheldon Bastacky, Julie Bergsten, Michael L Blute, Lori Boice, Roni J Bollag, Jeff Boyd, Erik Castle, Ying-Bei Chen, John Cheville, Erin Curley, Benjamin Davies, April DeVolk, Rajiv Dhir, Laura Dike, John Eckman, Jay Engel, Jodi Harr, Ronald Hrebinko, Mei Huang, Lori Huelsenbeck-Dill, Mary Iacocca, Bruce Jacobs, Michael Lobis, Jodi K Maranchie, Scott, Jerome Myers, Joel Nelson, Jeremy Parfitt, Anil Parwani, Nicholas Petrelli, Brenda Rabeno, Somak Roy, Andrew L Salner, Joel Slaton, Melissa Stanton, R Houston Thompson, Leigh Thorne, Kelinda Tucker, Paul M Weinberger, Cynthia Winemiller, Leigh Anne Zach, and Rosemary Zuna

    New England Journal of Medicine 374(2):135 (2016) PMID 26536169 PMCID PMC4775252

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is kno...
  10. Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway.

    Scientific reports 6:27391 (2016) PMID 27272709 PMCID PMC4895347

    Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A e...
  11. YAP/TAZ regulates the insulin signaling via IRS1/2 in endometrial cancer.

    American journal of cancer research 6(5):996 (2016) PMID 27293994 PMCID PMC4889715

    Insulin resistance (IR) is an important mechanism of pathogenesis of endometrial cancer (EC) and explains the pathogenic mechanism of high risk factors including Obesity BMI (body mass index), Type 2 Diabetes Mellitus, PCOS and so on. Relieving IR or inhibiting the function of insulin could be o...
  12. Glucose starvation induces mutation and lineage-dependent adaptive responses in a large collection of cancer cell lines.

    International Journal of Oncology 48(1):67 (2016) PMID 26573869 PMCID PMC4734611

    Tolerance of glucose deprivation is an important factor for cancer proliferation, survival, migration and progression. To systematically understand adaptive responses under glucose starvation in cancers, we analyzed reverse phase protein array (RPPA) data of 115 protein antibodies across a panel...
  13. Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm.

    American journal of cancer research 6(1):27 (2016) PMID 27073720 PMCID PMC4759394

    Yes-associated protein (YAP), the central mediator of Hippo pathway, not only regulates a diversity of cellular processes during development but also plays a pivotal role in tumorigenesis. YAP is overexpressed in many types of human cancers with its expression level being associated with patient...
  14. Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers.

    Cancer Cell 28(4):529 (2015) PMID 26461095 PMCID PMC4777353

    The discovery of long non-coding RNA (lncRNA) has dramatically altered our understanding of cancer. Here, we describe a comprehensive analysis of lncRNA alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across 13 cancer types from The Cancer Genome Atl...
  15. The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers.

    Cancer Cell 28(4):515 (2015) PMID 26439496 PMCID PMC4605878

    Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from...
  16. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.
    Daniel J Brat, Roel G W Verhaak, Kenneth D Aldape, W K Alfred Yung, Sofie R Salama, Lee A D Cooper, Esther Rheinbay, C Ryan Miller, Mark Vitucci, Olena Morozova, A Gordon Robertson, Houtan Noushmehr, Peter W Laird, Andrew D Cherniack, Rehan Akbani, Jason T Huse, Giovanni Ciriello, Laila M Poisson, Jill S Barnholtz-Sloan, Mitchel S Berger, Cameron Brennan, Rivka Colen, Howard Colman, Adam E Flanders, Caterina Giannini, Mia Grifford, Antonio Iavarone, Rajan Jain, Isaac Joseph, Jaegil Kim, Katayoon Kasaian, Tom Mikkelsen, Bradley A Murray, Brian Patrick O'Neill, Lior Pachter, Donald W Parsons, Carrie Sougnez, Erik P Sulman, Scott R Vandenberg, Erwin G Van Meir, Andreas von Deimling, Hailei Zhang, Daniel Crain, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Troy Shelton, Mark Sherman, Peggy Yena, Aaron Black, Jay Bowen, Katie Dicostanzo, Julie Gastier-Foster, Kristen M Leraas, Tara M Lichtenberg, Christopher R Pierson, Nilsa C Ramirez, Cynthia Taylor, Stephanie Weaver, Lisa Wise, Erik Zmuda, Tanja Davidsen, John A Demchok, Greg Eley, Martin L Ferguson, Carolyn M Hutter, Kenna R Mills Shaw, Bradley A Ozenberger, Margi Sheth, Heidi J Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean Claude Zenklusen, Brenda Ayala, Julien Baboud, Sudha Chudamani, Mark A Jensen, Jia Liu, Todd Pihl, Rohini Raman, Yunhu Wan, Ye Wu, Adrian Ally, J Todd Auman, Miruna Balasundaram, Saianand Balu, Stephen Baylin, Rameen Beroukhim, Moiz S Bootwalla, Reanne Bowlby, Christopher A Bristow, Denise Brooks, Yaron Butterfield, Rebecca Carlsen, Scott Carter, Lynda Chin, Andy Chu, Eric Chuah, Kristian Cibulskis, Amanda Clarke, Simon G Coetzee, Noreen Dhalla, Tim Fennell, Sheila Fisher, Stacey Gabriel, Gad Getz, Richard Gibbs, Ranabir Guin, Angela Hadjipanayis, D Neil Hayes, Toshinori Hinoue, Katherine Hoadley, Robert A Holt, Alan P Hoyle, Stuart R Jefferys, Steven Jones, Corbin D Jones, Raju Kucherlapati, Phillip H Lai, Eric Lander, Semin Lee, Lee Lichtenstein, Yussanne Ma, Dennis T Maglinte, Harshad S Mahadeshwar, Marco A Marra, Michael Mayo, Shaowu Meng, Matthew L Meyerson, Piotr A Mieczkowski, Richard A Moore, Lisle E Mose, Andrew J Mungall, Angeliki Pantazi, Michael Parfenov, Peter J Park, Joel S Parker, Charles M Perou, Alexei Protopopov, Xiaojia Ren, Jeffrey Roach, Thaís Sabedot, Jacqueline Schein, Steven E Schumacher, Jonathan G Seidman, Sahil Seth, Hui Shen, Janae V Simons, Payal Sipahimalani, Matthew G Soloway, Xingzhi Song, Huandong Sun, Barbara Tabak, Angela Tam, Donghui Tan, Jiabin Tang, Nina Thiessen, Timothy Triche, David J Van Den Berg, Umadevi Veluvolu, Scot Waring, Daniel J Weisenberger, Matthew D Wilkerson, Tina Wong, Junyuan Wu, Liu Xi, Andrew W Xu, Lixing Yang, Travis I Zack, Jianhua Zhang, B Arman Aksoy, Harindra Arachchi, Chris Benz, Brady Bernard, Daniel Carlin, Juok Cho, Daniel DiCara, Scott Frazer, Gregory N Fuller, Gao, Nils Gehlenborg, David Haussler, David I Heiman, Lisa Iype, Anders Jacobsen, Zhenlin Ju, Sol Katzman, Hoon Kim, Theo Knijnenburg, Richard Bailey Kreisberg, Michael S Lawrence, William Lee, Kalle Leinonen, Pei Lin, Shiyun Ling, Wenbin Liu, Yingchun Liu, Yuexin Liu, Yiling Lu, Gordon Mills, Sam Ng, Michael S Noble, Evan Paull, Arvind Rao, Sheila Reynolds, Gordon Saksena, Zack Sanborn, Chris Sander, Nikolaus Schultz, Yasin Senbabaoglu, Ronglai Shen, Ilya Shmulevich, Rileen Sinha, Josh Stuart, Onur Sumer, Yichao Sun, Natalie Tasman, Barry S Taylor, Doug Voet, Nils Weinhold, John N Weinstein, Da Yang, Kosuke Yoshihara, Siyuan Zheng, Wei Zhang, Lihua Zou, Ty Abel, Sara Sadeghi, Mark L Cohen, Jenny Eschbacher, Eyas M Hattab, Aditya Raghunathan, Matthew J Schniederjan, Dina Aziz, Gene Barnett, Wendi Barrett, Darell Bigner, Lori Boice, Cathy Brewer, Chiara Calatozzolo, Benito Campos, Carlos Gilberto Carlotti, Timothy A Chan, Lucia Cuppini, Erin Curley, Stefania Cuzzubbo, Karen Devine, Francesco DiMeco, Rebecca Duell, J Bradley Elder, Ashley Fehrenbach, Gaetano Finocchiaro, William Friedman, Jordonna Fulop, Johanna Gardner, Beth Hermes, Christel Herold-Mende, Christine Jungk, Ady Kendler, Norman Lehman, Eric Lipp, Ouida Liu, Randy Mandt, Mary McGraw, Roger Mclendon, Christopher McPherson, Luciano Neder, Phuong Nguyen, Ardene Noss, Raffaele Nunziata, Quinn T Ostrom, Cheryl Palmer, Alessandro Perin, Bianca Pollo, Alexander Potapov, Olga Potapova, W Kimryn Rathmell, Daniil Rotin, Lisa Scarpace, Cathy Schilero, Kelly Senecal, Kristen Shimmel, Vsevolod Shurkhay, Suzanne Sifri, Rosy Singh, Andrew E Sloan, Kathy Smolenski, Susan M Staugaitis, Ruth Steele, Leigh Thorne, Daniela P C Tirapelli, Andreas Unterberg, Mahitha Vallurupalli, Yun Wang, Ronald Warnick, Felicia Williams, Yingli Wolinsky, Sue Bell, Mara Rosenberg, Chip Stewart, Franklin Huang, Jonna L Grimsby, Amie J Radenbaugh, and Jianan Zhang

    New England Journal of Medicine 372(26):2481 (2015) PMID 26061751 PMCID PMC4530011

    Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to g...
  17. Development of a robust classifier for quality control of reverse-phase protein arrays.

    PMID 25380958 PMCID PMC4375399

    High-throughput reverse-phase protein array (RPPA) technology allows for the parallel measurement of protein expression levels in approximately 1000 samples. However, the many steps required in the complex protocol (sample lysate preparation, slide printing, hybridization, washing and amplified ...
  18. [Construction of novel thioredoxin fusion protein expression system and the production of recombinant Lf-CATH2].

    Chinese Journal of Biotechnology/Shengwu Gongch... 31(3):403 (2015) PMID 26204761

    The objective of this study was to construct an improved thioredoxin fusion protein expression system, and express the cathelicidin-derived peptide, Lf-CATH2. The improved fusion vector Lf-CATH2-pET32α(-TS) was successfully constructed by firstly deleting the thrombin site and S tag from the pET...
  19. Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks.

    Genome Research 25(2):257 (2015) PMID 25378249 PMCID PMC4315299

    We introduce a method for simultaneous prediction of microRNA-target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on microRNA-targ...
  20. α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration.

    Cancer Research 75(1):203 (2015) PMID 25503560 PMCID PMC4350791

    Metastatic cases of breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of α-tubulin acetylation are a sufficient cause of metastatic p...