KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET-expressing tumor cells
The MET receptor tyrosine kinase is often deregulated in human cancers and several MET inhibitors are evaluated in clinical trials. Similar to EGFR, MET signals through the RAS-RAF-ERK/MAPK pathway which plays key roles in cell proliferation and survival. Mutations of genes encoding for RAS proteins, particularly in KRAS, are commonly found in various tumors and are associated with constitutive activation of the MAPK pathway. It was shown for EGFR, that KRAS mutations render upstream EGFR inhibition ineffective in EGFR-positive colorectal cancers. (Source: Molecular Oncology)
Source: Molecular Oncology - April 13, 2015 Category: Cancer & Oncology Authors: Dominic Leiser, Michaela Medová, Kei Mikami, Lluís Nisa, Deborah Stroka, Andree Blaukat, Friedhelm Bladt, Daniel M. Aebersold, Yitzhak Zimmer Source Type: research
Natural product (−)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1
Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21WAF−1. We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cel...
Source: Molecular Oncology - April 9, 2015 Category: Cancer & Oncology Authors: Lan Lan, Carl Appelman, Amber R. Smith, Jia Yu, Sarah Larsen, Rebecca T. Marquez, Hao Liu, Xiaoqing Wu, Philip Gao, Anuradha Roy, Asokan Anbanandam, Ragul Gowthaman, John Karanicolas, Roberto N. De Guzman, Steven Rogers, Jeffrey Aubé, Min Ji, Robert S. C Source Type: research
Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation
AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. (Source: Molecular Oncology)
Source: Molecular Oncology - April 9, 2015 Category: Cancer & Oncology Authors: E.Merit Reyes-Reyes, Francesca R. Šalipur, Mitra Shams, Matthew K. Forsthoefel, Paula J. Bates Source Type: research
Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation
AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. (Source: Molecular Oncology)
Source: Molecular Oncology - April 9, 2015 Category: Cancer & Oncology Authors: E.Merit Reyes-Reyes, Francesca R. Šalipur, Mitra Shams, Matthew K. Forsthoefel, Paula J. Bates Source Type: research
miRNA-221 and miRNA-222 induce apoptosis via the KIT/AKT signalling pathway in gastrointestinal stromal tumours
This study aimed at evaluating the miR-221 and miR-222 expression profiles in different GIST subtypes and the functional role of these miRNAs. Expression of miR-221 and miR-222 was analysed in six KIT exon 9 and three KIT exon 11 mutated and nine wildtype GISTs by qPCR. (Source: Molecular Oncology)
Source: Molecular Oncology - April 9, 2015 Category: Cancer & Oncology Authors: Michaela Angelika Ihle, Marcel Trautmann, Helen Kuenstlinger, Sebastian Huss, Carina Heydt, Jana Fassunke, Eva Wardelmann, Sebastian Bauer, Hans-Ulrich Schildhaus, Reinhard Buettner, Sabine Merkelbach-Bruse Source Type: research
Natural product (–)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1
Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21WAF-1. We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cells...
Source: Molecular Oncology - April 9, 2015 Category: Cancer & Oncology Authors: Lan Lan, Carl Appelman, Amber R. Smith, Jia Yu, Sarah Larsen, Rebecca T. Marquez, Hao Liu, Xiaoqing Wu, Philip Gao, Anuradha Roy, Asokan Anbanandam, Ragul Gowthaman, John Karanicolas, Roberto N. De Guzman, Steven Rogers, Jeffrey Aubé, Min Ji, Robert S. C Source Type: research
Gene expression profiling of sequential metastatic biopsies for biomarker discovery in breast cancer
The feasibility of longitudinal metastatic biopsies for gene expression profiling in breast cancer is unexplored. Dynamic changes in gene expression can potentially predict efficacy of targeted cancer drugs.Patients enrolled in a phase III trial of metastatic breast cancer with docetaxel monotherapy versus combination of docetaxel + sunitinib were offered to participate in a translational substudy comprising longitudinal fine needle aspiration biopsies and Positron Emission Tomography imaging before (T1) and two weeks after start of treatment (T2). (Source: Molecular Oncology)
Source: Molecular Oncology - April 2, 2015 Category: Cancer & Oncology Authors: Theodoros Foukakis, John Lövrot, Patricia Sandqvist, Hanjing Xie, Linda S. Lindström, Carla Giorgetti, Hans Jacobsson, Elham Hedayati, Jonas Bergh Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - April 1, 2015 Category: Cancer & Oncology Source Type: research
Upregulated interleukin-6 expression contributes to erlotinib resistance in head and neck squamous cell carcinoma
Despite the role of epidermal growth factor receptor (EGFR) signaling in head and neck squamous cell carcinoma (HNSCC) development and progression, clinical trials involving EGFR tyrosine kinase inhibitors (TKIs) have yielded poor results in HNSCC patients. Mechanisms of acquired resistance to the EGFR TKI erlotinib was investigated by developing erlotinib-resistant HNSCC cell lines and comparing their gene expression profiles with their parental erlotinib-sensitive HNSCC cell lines using microarray analyses and subsequent pathway and network analyses. (Source: Molecular Oncology)
Source: Molecular Oncology - April 1, 2015 Category: Cancer & Oncology Authors: Aditya Stanam, Laurie Love-Homan, Tisha S. Joseph, Madelyn Espinosa-Cotton, Andrean L. Simons Source Type: research
Preclinical Validation of Anti-Nuclear Factor-kappa B Therapy to Inhibit Human Vestibular Schwannoma Growth
Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non-existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explored in VS. A bioinformatic network analysis of all genes reported to be differentially expressed in human VS revealed a pro-inflammatory transcription factor nuclear factor-kappa B (NF-κB) as a central molecule in VS pathobiology. (Source: Molecular Oncology)
Source: Molecular Oncology - March 31, 2015 Category: Cancer & Oncology Authors: Sonam Dilwali, Martijn C. Briët, Shyan-Yuan Kao, Takeshi Fujita, Lukas D. Landegger, Michael P. Platt, Konstantina M. Stankovic Source Type: research
Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma
Multiple myeloma (MM) is an aggressive incurable plasma cell malignancy with a median life expectancy of less than seven years. Antibody-based therapies have demonstrated substantial clinical benefit for patients with hematological malignancies, particular in B cell Non-Hodgkin’s lymphoma. The lack of immunotherapies specifically targeting MM cells led us to develop a human-mouse chimeric antibody directed against the B cell maturation antigen (BCMA), which is almost exclusively expressed on plasma cells and multiple myeloma cells. (Source: Molecular Oncology)
Source: Molecular Oncology - March 31, 2015 Category: Cancer & Oncology Authors: Felix Oden, Stephen F. Marino, Janko Brand, Susanne Scheu, Cathleen Kriegel, Daniel Olal, Anna Takvorian, Jörg Westermann, Buket Yilmaz, Michael Hinz, Oliver Daumke, Uta E. Höpken, Gerd Müller, Martin Lipp Source Type: research
KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer
The KRAS gene frequently mutates in colorectal cancer (CRC). Here we investigated the prognostic and predictive role of KRAS mutation in patients with stage II or III CRC. (Source: Molecular Oncology)
Source: Molecular Oncology - March 26, 2015 Category: Cancer & Oncology Authors: Yanhong Deng, Li Wang, Shuyun Tan, George P. Kim, Ruoxu Dou, Dianke Chen, Yue Cai, Xinhui Fu, Lei Wang, Jun Zhu, Jianping Wang Source Type: research
Comprehensive analysis of microRNA expression profile in malignant glioma tissues
Malignant gliomas represent the most devastating group of brain tumors in adults, among which glioblastoma multiforme (GBM) exhibits the highest malignancy rate. Despite combined modality treatment, GBM recurs and is invariably fatal. A further insight into the molecular background of gliomagenesis is required to improve patient outcomes. The primary aim of this study was to gain broad information on the miRNA expression pattern in malignant gliomas, mainly GBM. We investigated the global miRNA profile of malignant glioma tissues with miRNA microarrays, deep sequencing and meta-analysis. (Source: Molecular Oncology)
Source: Molecular Oncology - March 26, 2015 Category: Cancer & Oncology Authors: Monika Piwecka, Katarzyna Rolle, Agnieszka Belter, Anna Maria Barciszewska, Marek Żywicki, Marcin Michalak, Stanisław Nowak, Mirosława Z. Naskręt-Barciszewska, Jan Barciszewski Source Type: research
MicroRNA-135b regulates ERα, AR and HIF1AN and affects breast and prostate cancer cell growth
MicroRNAs (miRNAs) regulate a wide range of cellular signaling pathways and biological processes in both physiological and pathological states such as cancer. We have previously identified miR-135b as a direct regulator of androgen receptor (AR) protein level in prostate cancer (PCa). We wanted to further explore the relationship of miR-135b to hormonal receptors, particularly estrogen receptor α (ERα). Here we show that miR-135b expression is lower in ERα-positive breast tumors as compared to ERα-negative samples in two independent breast cancer (BCa) patient cohorts (101 and 1302 samples). (Source: Molecular Oncology)
Source: Molecular Oncology - March 25, 2015 Category: Cancer & Oncology Authors: Anna Aakula, Suvi-Katri Leivonen, Petteri Hintsanen, Tero Aittokallio, Yvonne Ceder, Anne-Lise Børresen-Dale, Merja Perälä, Päivi Östling, Olli Kallioniemi Source Type: research
Plasma membrane gp96 enhances invasion and metastatic potential of liver cancer via regulation of uPAR
Targeted therapy is currently under intensive investigation due to the resistance of liver cancer to cytotoxic chemotherapies. Dissecting the molecular events that drive the progression of liver cancer and defining specific targets are urgently needed to develop efficient tailored therapies. Cell membrane gp96 (mgp96) has been implicated in tumor growth and malignancy. Here, we explored the functional and clinical relevance of mgp96 in liver cancer. We found that elevated mgp96 abundance was associated with tumor metastasis and recurrence in patients with primary liver tumors. (Source: Molecular Oncology)
Source: Molecular Oncology - March 24, 2015 Category: Cancer & Oncology Authors: Junwei Hou, Xin Li, Changfei Li, Lu Sun, Yulai Zhao, Jingmin Zhao, Songdong Meng Source Type: research
