Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells
Cell migration and invasion are highly regulated processes involved in both physiological and pathological conditions. Here we show that autophagy modulation regulates the migration and invasion capabilities of glioblastoma (GBM) cells. We observed that during autophagy occurrence, obtained by nutrient deprivation or by pharmacological inhibition of the mTOR complexes, GBM migration and chemokine-mediated invasion were both impaired. We also observed that SNAIL and SLUG, two master regulators of the epithelial-mesenchymal transition (EMT process), were down-regulated upon autophagy stimulation and, as a consequence, we fou...
Source: Molecular Oncology - May 12, 2015 Category: Cancer & Oncology Authors: Myriam Catalano, Giuseppina D’Alessandro, Francesca Lepore, Marco Corazzari, Sara Caldarola, Cristina Valacca, Fiorella Faienza, Vincenzo Esposito, Cristina Limatola, Francesco Cecconi, Sabrina Di Bartolomeo Source Type: research
CCR9-mediated Signaling through β-catenin and Identification of a Novel CCR9 Antagonist
In this study, we characterized a novel CCR9-mediated pathway that promotes pancreatic cancer cell invasion and drug resistance, indicating that CCR9 may play a critical role in cancer progression through activation of β-catenin. We noted that the CCL25/CCR9 axis in pancreatic cancer cells induced the activation of β-catenin, which enhanced cell proliferation, invasion, and drug resistance. (Source: Molecular Oncology)
Source: Molecular Oncology - May 11, 2015 Category: Cancer & Oncology Authors: Sangjun Lee, Eileen L. Heinrich, Lily Li, Jianming Lu, Audrey H. Choi, Rachel A. Levy, Jeffrey E. Wagner, M.L. Richard Yip, Nagarajan Vaidehi, Joseph Kim Source Type: research
TIPIN depletion leads to apoptosis in breast cancer cells
Triple-negative breast cancer (TNBC) is the breast cancer subgroup with the most aggressive clinical behavior. Alternatives to conventional chemotherapy are required to improve the survival of TNBC patients. Gene-expression analyses for different breast cancer subtypes revealed significant overexpression of the Timeless-interacting protein (TIPIN), which is involved in the stability of DNA replication forks, in the highly proliferative associated TNBC samples. Immunohistochemistry analysis showed higher expression of TIPIN in the most proliferative and aggressive breast cancer subtypes including TNBC, and no TIPIN expressi...
Source: Molecular Oncology - May 8, 2015 Category: Cancer & Oncology Authors: Céline Baldeyron, Amélie Brisson, Bruno Tesson, Fariba Némati, Stéphane Koundrioukoff, Elie Saliba, Leanne De Koning, Elise Martel, Mengliang Ye, Guillem Rigaill, Didier Meseure, André Nicolas, David Gentien, Didier Decaudin, Michelle Debatisse, Sté Source Type: research
Concomitant inactivation of the p53- and pRB- functional pathways predicts resistance to DNA damaging drugs in breast cancer
Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance to DNA damaging drugs in breast cancer better than TP53 mutations alone. Further, we hypothesized that redundant pathway(s) may compensate for loss of p53-pathway signaling and that these are inactivated as well in resistant tumour ...
Source: Molecular Oncology - May 7, 2015 Category: Cancer & Oncology Authors: Stian Knappskog, Elisabet O. Berge, Ranjan Chrisanthar, Stephanie Geisler, Vidar Staalesen, Beryl Leirvaag, Synnøve Yndestad, Elise de Faveri, Bård O. Karlsen, David C. Wedge, Lars A. Akslen, Peer K. Lilleng, Erik Løkkevik, Steinar Lundgren, Bjørn Ø Source Type: research
Concomitant inactivation of the p53- and pRB functional pathways predicts resistance to DNA damaging drugs in breast cancer
Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance to DNA damaging drugs in breast cancer better than TP53 mutations alone. Further, we hypothesized that redundant pathway(s) may compensate for loss of p53-pathway signaling and that these are inactivated as well in resistant tumour ...
Source: Molecular Oncology - May 7, 2015 Category: Cancer & Oncology Authors: Stian Knappskog, Elisabet O. Berge, Ranjan Chrisanthar, Stephanie Geisler, Vidar Staalesen, Beryl Leirvaag, Synnøve Yndestad, Elise de Faveri, Bård O. Karlsen, David Wedge, Lars A. Akslen, Peer K. Lilleng, Erik Løkkevik, Steinar Lundgren, Bjørn Østen Source Type: research
Concomitant inactivation of the p53-and pRB Functional Pathways Predicts Resistance to DNA damaging drugs in Breast Cancer
Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance to DNA damaging drugs in breast cancer better than TP53 mutations alone. Further, we hypothesized that redundant pathway(s) may compensate for loss of p53-pathway signaling and that these are inactivated as well in resistant tumour ...
Source: Molecular Oncology - May 7, 2015 Category: Cancer & Oncology Authors: Stian Knappskog, Elisabet O. Berge, Ranjan Chrisanthar, Stephanie Geisler, Vidar Staalesen, Beryl Leirvaag, Synnøve Yndestad, Elise de Faveri, Bård O. Karlsen, David Wedge, Lars A. Akslen, Peer K. Lilleng, Erik Løkkevik, Steinar Lundgren, Bjørn Østen Source Type: research
Genome Methylation Patterns in Male Breast Cancer – Identification of an Epitype with Hypermethylation of Polycomb Target Genes
Male breast cancer (MBC) is a rare disease that shares both similarities and differences with female breast cancer (FBC). Very few genetic studies have been performed on MBC and global DNA methylation patterns in MBC have to date not been studied. Epigenetic changes are known to be involved in tumorigenesis; methylation may influence the expression of cancer-related genes, which may be potential druggable targets.The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups in MBC, luminal M1 and M2, as well as the intrinsic subgrou...
Source: Molecular Oncology - May 7, 2015 Category: Cancer & Oncology Authors: Ida Johansson, Martin Lauss, Karolina Holm, Johan Staaf, Cecilia Nilsson, Marie-Louise Fjällskog, Markus Ringnér, Ingrid Hedenfalk Source Type: research
Oncolytic Vaccinia Virus Synergizes with Irinotecan in Colorectal Cancer
Metastatic colorectal cancer (CRC) is complex clinical challenge for which there are limited treatment options. Chemotherapy with or without surgery provides moderate improvements in overall survival and quality of life; nevertheless the 5-year survival remains below 30%. Oncolytic vaccinia virus (VV) therapy has shown strong anti-tumour activity in orthotopic murine models of CRC, however transient delays in disease progression are insufficient to lead to long-term survival. Here we examined the efficacy of combining VV with oxaliplatin or SN38 (active metabolite of irinotecan) in three CRC cell lines in vitro and VV with...
Source: Molecular Oncology - May 6, 2015 Category: Cancer & Oncology Authors: Kathryn Ottolino-Perry, Sergio A. Acuna, Fernando A. Angarita, Clara Sellers, Siham Zerhouni, Nan Tang, J.Andrea McCart Source Type: research
-like signature in triple negative breast cancer: molecular and clinical characterization reveals subgroups with therapeutic potential
Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10–15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. (Source: Molecular Oncology)
Source: Molecular Oncology - May 6, 2015 Category: Cancer & Oncology Authors: Tesa M. Severson, Justine Peeters, Ian Majewski, Magali Michaut, Astrid Bosma, Philip C. Schouten, Suet-Feung Chin, Bernard Pereira, Mae A. Goldgraben, Tycho Bismeijer, Roelof J.C. Kluin, Jettie J.F. Muris, Karin Jirström, Ron M. Kerkhoven, Lodewyk Wesse Source Type: research
Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP-dependent Mkl1 signaling
Radiotherapy is a standard treatment after conservative breast cancer surgery. Clinical and experimental evidence indicates that patients with local breast cancer relapse within a previously irradiated area have an increased risk of distant metastasis formation. The mechanisms responsible for the increased aggressiveness remain to be fully understood. In the present study, we used the clinically relevant 4T1 breast cancer model mimicking aggressive local relapse after radiotherapy to identify differences between tumors grown in untreated versus preirradiated mammary glands. (Source: Molecular Oncology)
Source: Molecular Oncology - April 29, 2015 Category: Cancer & Oncology Authors: Maria B. Asparuhova, Chiara Secondini, Curzio Rüegg, Ruth Chiquet-Ehrismann Source Type: research
Pathway-based personalized analysis of breast cancer expression data
Analysis of high throughput data on cancer primarily uses an “atomistic” approach, representing a tumor in terms of single-gene properties. Furthermore, very little if any prior knowledge is incorporated in the analysis. Several recently introduced methods advocate characterization of a tumor in terms of “coarse grained” pathway-based variables. A very extensive recent study on breast cancer provides an excellent testing ground for these methods; in particular, of their robustness and ability to discover new knowledge and insights. (Source: Molecular Oncology)
Source: Molecular Oncology - April 29, 2015 Category: Cancer & Oncology Authors: Anna Livshits, Anna Git, Garold Fuks, Carlos Caldas, Eytan Domany Source Type: research
Thymosin-β4 is a determinant of drug sensitivity for Fenretinide and Vorinostat combination therapy in neuroblastoma
Retinoids are an important component of neuroblastoma therapy at the stage of minimal residual disease, yet 40-50% of patients treated with 13-cis-retinoic acid (13-cis-RA) still relapse, indicating the need for more effective retinoid therapy. Vorinostat, or Suberoylanilide hydroxamic acid (SAHA), is a potent inhibitor of histone deacetylase (HDAC) classes I & II and has antitumor activity in vitro and in vivo. Fenretinide (4-HPR) is a synthetic retinoid which acts on cancer cells through both nuclear retinoid receptor and non-receptor mechanisms. (Source: Molecular Oncology)
Source: Molecular Oncology - April 28, 2015 Category: Cancer & Oncology Authors: Belamy B. Cheung, Owen Tan, Jessica Koach, Bing Liu, Michael SY. Shum, Daniel R. Carter, Selina Sutton, Sela T. Po’uha, Louis Chesler, Michelle Haber, Murray D. Norris, Maria Kavallaris, Tao Liu, Geraldine M. O’Neill, Glenn M. Marshall Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - April 27, 2015 Category: Cancer & Oncology Source Type: research
Diphtheria-toxin based anti-human CCR4 immunotoxin for targeting human CCR4 cells
In this study we have successfully developed three versions of diphtheria-toxin based anti-human CCR4 immunotoxins (monovalent, bivalent and single-chain fold-back diabody). (Source: Molecular Oncology)
Source: Molecular Oncology - April 25, 2015 Category: Cancer & Oncology Authors: Zhaohui Wang, Min Wei, Huiping Zhang, Hongyuan Chen, Sharon Germana, Christene A. Huang, Joren C. Madsen, David H. Sachs, Zhirui Wang Source Type: research
Targeting Histone Deacetylase 6 mediates a dual anti-melanoma effect: enhanced antitumor immunity and impaired cell proliferation
The median survival for metastatic melanoma is in the realm of 8-16 months and there are few therapies that offer significant improvement in overall survival. One of the recent advances in cancer treatment focuses on epigenetic modifiers to alter the survivability and immunogenicity of cancer cells. Our group and others have previously demonstrated that pan-HDAC inhibitors induce apoptosis, cell cycle arrest and changes in the immunogenicity of melanoma cells. Here we interrogated specific HDACs which may be responsible for this effect. (Source: Molecular Oncology)
Source: Molecular Oncology - April 23, 2015 Category: Cancer & Oncology Authors: K.V. Woan, M. Lienlaf, P. Perez-Villaroel, C. Lee, F. Cheng, T. Knox, D.M. Woods, K. Barrios, J. Powers, E. Sahakian, H.W. Wang, J. Canales, D. Marante, K.S.M. Smalley, J. Bergman, E. Seto, A. Kozikowski, J. Pinilla-Ibarz, A. Sarnaik, E. Celis, J. Weber, Source Type: research
