Digital Commons Network^™

Printing The Pathway Forward In Bone Metastatic Cancer Research: Applications Of 3d Engineered Models And Bioprinted Scaffolds To Recapitulate The Bone-Tumor Niche., Anne M. Hughes, Alexus D. Kolb, Alison B. Shupp, Kristy M. Shine, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone-tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. …

Microrna And Transcription Factor Co-Regulatory Networks And Subtype Classification Of Seminoma And Non-Seminoma In Testicular Germ Cell Tumors., Guimin Qin, Saurav Mallik, Ramkrishna Mitra, Aimin Li, Peilin Jia, Christine M. Eischen, Zhongming Zhao

Department of Cancer Biology Faculty Papers

Recent studies have revealed that feed-forward loops (FFLs) as regulatory motifs have synergistic roles in cellular systems and their disruption may cause diseases including cancer. FFLs may include two regulators such as transcription factors (TFs) and microRNAs (miRNAs). In this study, we extensively investigated TF and miRNA regulation pairs, their FFLs, and TF-miRNA mediated regulatory networks in two major types of testicular germ cell tumors (TGCT): seminoma (SE) and non-seminoma (NSE). Specifically, we identified differentially expressed mRNA genes and miRNAs in 103 tumors using the transcriptomic data from The Cancer Genome Atlas. Next, we determined significantly correlated TF-gene/miRNA and miRNA-gene/TF …

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 …

Minimal Information For Studies Of Extracellular Vesicles 2018 (Misev2018): A Position Statement Of The International Society For Extracellular Vesicles And Update Of The Misev2014 Guidelines, Clotilde Théry, Kenneth W. Witwer, Elena Aikawa, Maria Jose Alcaraz, Johnathon D. Anderson, Ramaroson Andriantsitohaina, Anna Antoniou, Tanina Arab, Fabienne Archer, Georgia K. Atkiin-Smith, D. Craig Ayre, Jean-Marie Bach, Daniel Bachurski, Hossein Baharvand, Leonora Balaj, Shawn Baldacchino, Natalie N. Bauer, Amy A. Baxter, Mary Bebawy, Carla Beckham, Apolonija Bedina Zavec, Abderrahim Benmoussa, Anna C. Berardi, Paolo Bergese, Ewa Bielska, Cherie Blenkiron, Sylwia Bobis-Wozowicz, Eric Boilard, Wilfrid Boireau, Antonella Bongiovanni, Francesc E. Borràs, Steffi Bosch, Chantal M. Boulanger, Xandra Breakefield, Andrew M. Breglio, Meadhbh Á. Brennan, David R. Brigstock, Alain Brisson, Marike L.D. Broekman, Jacqueline F. Bromberg, Paulina Bryl-Górecka, Shilpa Buch, Amy H. Buck, Dylan Burger, Sara Busatto, Dominik Buschmann, Benedetta Bussolati, Edit I. Buzás, James Bryan Byrd, Giovanni Camussi, David R.F. Carter, Sarah Caruso, Lawrence W. Chamley, Yu-Ting Chang, Chichen Chen, Shuai Chen, Lesley Cheng, Andrew R. Chin, Aled Clayton, Stefano P. Clerici, Alex Cocks, Emanuele Cocucci, Robert J. Coffey, Anabela Cordeiro-Da-Silva, Yvonne Couch, Frank A.W. Coumans, Beth Coyle, Rossella Crescitelli, Miria Ferreira Criado, Crislyn D’ Souza-Schorey, Saumya Das, Amrita Datta Chaudhuri, Paola De Candia, Eliezer F. De Santana Junior, Olivier De Wever, Hernando A. Del Portillo, Tanguy Demaret, Sarah Deville, Andrew Devitt, Bert Dhondt, Dolores Di Vizio, Lothar C. Dieterich, Vincenza Dolo, Ana Paula Dominguez Rubio, Massimo Dominici, Mauricio R. Dourado, Tom A.P Driedonks, Filipe V. Duarte, Heather M. Duncan, Ramon M. Eichenberger, Karin Ekström, Samir El Andaloussi, Celine Elie-Caille, Uta Erdbrügger, Juan M. Falcón-Pérez, Farah Fatima, Jason E. Fish, Miguel Flores-Bellver, András Försönits, Annie Frelet-Barrand, Fabia Fricke, Gregor Fuhrmann, Susanne Gabrielsson, Ana Gámez-Valero, Chris Gardiner, Kathrin Gärtner, Raphael Gaudin, Yong Song Gho, Bernd Giebel, Caroline Gilbert, Mario Gimona, Ilaria Giusti, Deborah C.I. Goberdhan, André Görgens, Sharon M. Gorski, David W. Greening, Julia Christina Gross, Alice Gualerzi, Gopal N. Gupta, Dakota Gustafson, Aase Handberg, Reka A. Haraszti, Paul Harrison, Hargita Hegyesi, An Hendrix, Andrew F. Hill, Fred H. Hochberg, Karl F. Hoffmann, Beth Holder, Harry Holthofer, Baharak Hosseinkhani, Guoku Hu, Yiyao Huang, Veronica Huber, Stuart Hunt, Ahmed Gamal-Eldin Ibrahim, Tsuneya Ikezu, Jameel M. Inal, Mustafa Isin, Alena Ivanova, Hannah K. Jackson, Soren Jacobsen, Steven M. Jay, Muthuvel Jayachandran, Guido Jenster, Lanzhou Jiang, Suzanne M. Johnson, Jennifer C. Jones, Ambrose Jong, Tijana Jovanovic-Talisman, Stephanie Jung, Raghu Kalluri, Shin-Ichi Kano, Sukhbir Kaur, Yumi Kawamura, Evan T. Keller, Delaram Khamari, Elena Khomyakova, Anastasia Khvorova, Peter Kierulf, Kwang Pyo Kim, Thomas Kislinger, Mikael Klingeborn, David J. Klinke Ii, Miroslaw Kornek, Maja M. Kosanović, Árpád Ferenc Kovács, Eva-Maria Krämer-Albers, Susanne Krasemann, Mirja Krause, Igor V. Kurochkin, Gina D. Kusuma, Sören Kuypers, Saara Laitinen, Scott M. Langevin, Lucia R. Languino, Joanne Lannigan, Cecilia Lässer, Louise C. Laurent, Gregory Lavieu, Elisa Lázaro-Ibáñez, Soazig Le Lay, Myung-Shin Lee, Yi Xin Fiona Lee, Debora S. Lemos, Metka Lenassi, Aleksandra Leszczynska, Isaac T.S. Li, Ke Liao, Sten F. Libregts, Erzsebet Ligeti, Rebecca Lim, Sai Kiang Lim, Aija Linē, Karen Linnemannstöns, Alicia Llorente, Catherine A. Lombard, Magdalena J. Lorenowicz, Ákos M. Lörincz, Jan Lötvall, Jason Lovett, Michelle C. Lowry, Xavier Loyer, Quan Lu, Barbara Lukomska, Taral R. Lunavat, Sybren L.N. Maas, Harmeet Malhi, Antonio Marcilla, Jacopo Mariani, Javier Mariscal, Elena S. Martens-Uzunova, Lorena Martin-Jaular, M. Carmen Martinez, Vilma Regina Martins, Mathilde Mathieu, Suresh Mathivanan, Marco Maugeri, Lynda K. Mcginnis, Mark J. Mcvey, David G. Meckes, Jr., Katie L. Meehan, Inge Mertens, Valentina R. Minciacchi, Andreas Möller, Malene Møller Jørgensen, Aizea Morales-Kastresana, Jess Morhayim, François Mullier, Maurizio Muraca, Luca Musante, Veronika Mussack, Dillon C. Muth, Kathryn H. Myburgh, Tanbir Najrana, Muhammad Nawaz, Irina Nazarenko, Peter Nejsum, Christian Neri, Tommaso Neri, Rienk Nieuwland, Leonardo Nimrichter, John P. Nolan, Esther N.M. Nolte-’ T Hoen, Nicole Noren Hooten, Lorraine O’Driscoll, Tina O’Grady, Ana O’Loghlen, Takahiro Ochiya, Martin Olivier, Alberto Ortiz, Luis A. Ortiz, Xabier Osteikoetxea, Ole Ostegaard, Matias Ostrowski, Jaesung Park, D. Michiel Pegtel, Hector Peinado, Francesca Perut, Michael W. Pfaffl, Donald G. Phinney, Bartijn C.H. Pieters, Ryan C. Pink, David S. Pisetsky, Elke Pogge Von Strandmann, Iva Polakovicova, Ivan K.H. Poon, Bonita H. Powell, Ilaria Prada, Lynn Pulliam, Peter Quesenberry, Annalisa Radeghieri, Robert L. Raffai, Stefania Raimondo, Janusz Rak, Marcel I. Ramirez, Graça Raposo, Morsi S. Rayyan, Neta Regev-Rudzki, Fran L. Ricklefs, Paul D. Robbins, David D. Roberts, Silvia C. Rodrigues, Eva Rohde, Sophie Rome, Kasper M.A. Rouschop, Aurelia Rughetti, Ashley E. Russell, Paula Saá, Susmita Sahoo, Edison Salas-Huenuleo, Catherine Sánchez, Julie A. Saugstad, Meike J. Saul, Raymond M. Schiffelers, Raphael Schneider, Tine Hiorth Schøyen, Aaron Scott, Eriomina Shahaj, Shivani Sharma, Olga Shatnyeva, Faezeh Shekari, Ganesh Vilas Shelke, Ashok K. Shetty, Kiyotaka Shiba, Pia R-M Siljander, Andreia M. Silva, Agata Skowronek, Orman L. Snyder Ii, Rodrigo Pedro Soares, Barbara W. Sódar, Carolina Soekmadji, Javier Sotillo, Philip D. Stahl, Willem Stoorvogel, Shannon L. Stott, Erwin F. Strasser, Simon Swift, Hidetoshi Tahara, Muneesh Tewari, Kate Timms, Swasti Tiwari, Rochelle Tixeira, Mercedes Tkach, Wei Seong Toh, Richard Tomasini, Ana Claudia Torrecilhas, Juan Pablo Tosar, Vasilis Toxavidis, Lorena Urbanelli, Pieter Vader, Bas W.M. Van Balkom, Susanne G. Van Der Grein, Jan Van Deun, Martijn J.C. Van Herwijnen, Kendall Van Keuren-Jensen, Guillaume Van Niel, Martin E. Van Royen, Andre J. Van Wijnen, M. Helena Vasconcelos, Ivan J. Vechetti Jr., Tiago D. Veit, Laura J. Vella, Émilie Velot, Frederik J. Verweij, Beate Vestad, Jose L. Viñas, Tamás Visnovitz, Krisztina V. Vukman, Jessica Wahlgren, Dionysios C. Watson, Marca H.M. Wauben, Alissa Weaver, Jason P. Webber, Viktoria Weber, Ann M. Wehman, Daniel J. Weiss, Joshua A. Welsh, Sebastian Wendt, Asa M. Wheelock, Zoltán Wiener, Leonie Witte, Joy Wolfram, Angeliki Xagorari, Patricia Xander, Jing Xu, Xiaomei Yan, María Yáñez-Mó, Hang Yin, Yuana Yuana, Valentina Zappulli, Jana Zarubova, Vytautas Žėkas, Jian-Ye Zhang, Zezhou Zhao, Lei Zheng, Alexander R. Zheutlin, Antje M. Zickler, Pascale Zimmermann, Angela M. Zivkovic, Davide Zocco, Ewa K. Zuba-Surma

Department of Cancer Biology Faculty Papers

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines …

A Neuronal Network Of Mitochondrial Dynamics Regulates Metastasis., M. Cecilia Caino, Jae Ho Seo, Angeline Aguinaldo, Eric Wait, Kelly G. Bryant, Andrew V. Kossenkov, James E. Hayden, Valentina Vaira, Annamaria Morotti, Stefano Ferrero, Silvano Bosari, Dmitry I. Gabrilovich, Lucia R. Languino, Andrew R. Cohen, Dario C. Altieri

Department of Cancer Biology Faculty Papers

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater …

Expression Of Μ-Protocadherin Is Negatively Regulated By The Activation Of The Β-Catenin Signaling Pathway In Normal And Cancer Colorectal Enterocytes., Lucia Montorsi, Sandra Parenti, Lorena Losi, Fabrizio Ferrarini, Claudia Gemelli, A Rossi, Gianrocco Manco, Stefano Ferrari, Bruno Calabretta, Enrico Tagliafico, Tommaso Zanocco-Marani, Alexis Grande

Department of Cancer Biology Faculty Papers

Mu-protocadherin (MUCDHL) is an adhesion molecule predominantly expressed by colorectal epithelial cells which is markedly downregulated upon malignant transformation. Notably, treatment of colorectal cancer (CRC) cells with mesalazine lead to increased expression of MUCDHL, and is associated with sequestration of β-catenin on the plasma membrane and inhibition of its transcriptional activity. To better characterize the causal relationship between β-catenin and MUCDHL expression, we performed various experiments in which CRC cell lines and normal colonic organoids were subjected to culture conditions inhibiting (FH535 treatment, transcription factor 7-like 2 siRNA inactivation, Wnt withdrawal) or stimulating (LiCl treatment) β-catenin activity. We show here …

Deregulation Of Mir-34b/Sox2 Predicts Prostate Cancer Progression., Irene Forno, Stefano Ferrero, Maria Veronica Russo, Giacomo Gazzano, Sara Giangiobbe, Emanuele Montanari, Alberto Del Nero, Bernardo Rocco, Giancarlo Albo, Lucia R Languino, Dario C Altieri, Valentina Vaira, Silvano Bosari

Department of Cancer Biology Faculty Papers

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was …

Novel Actions Of Next-Generation Taxanes Benefit Advanced Stages Of Prostate Cancer., Renée De Leeuw, Lisa D. Berman-Booty, Matthew J. Schiewer, Stephen J Ciment, Robert Den, Adam P. Dicker, William Kelly, Edouard J. Trabulsi, Costas D. Lallas, Leonard G. Gomella, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond.

EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro …

Targeting Cell Cycle And Hormone Receptor Pathways In Cancer., C E S Comstock, M A Augello, J F Goodwin, R De Leeuw, M J Schiewer, W F Ostrander, R A Burkhart, A K Mcclendon, Peter Mccue, Edouard J. Trabulsi, Costas D. Lallas, Leonard G Gomella, Md, M M Centenera, Jonathan Brody, Md, L M Butler, W D Tilley, K E Knudsen, Phd

Department of Cancer Biology Faculty Papers

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability …