A Novel Functional Splice Variant of AKT3 Defined by Analysis of Alternative Splice Expression in HPV-Positive Oropharyngeal Cancers
In this study, we sought to analyze alternative splicing events (ASE) that could alter gene function independent of mutations. To identify ASE unique to HPV-related tumors, RNA sequencing was performed on 46 HPV-positive OPSCC and 25 normal tissue samples. A novel algorithm using outlier statistics on RNA-sequencing junction expression identified 109 splicing events, which were confirmed in a validation set from The Cancer Genome Atlas. Because the most common type of splicing event identified was an alternative start site (39%), MBD-seq genome-wide CpG methylation data were analyzed for methylation alterations at promoter...
Source: Cancer Research - October 1, 2017 Category: Cancer & Oncology Authors: Theresa Guo, Akihiro Sakai, Bahman Afsari, Michael Considine, Ludmila Danilova, Alexander V. Favorov, Srinivasan Yegnasubramanian, Dylan Z. Kelley, Emily Flam, Patrick K. Ha, Zubair Khan, Sarah J. Wheelan, J. Silvio Gutkind, Elana J. Fertig, Daria A. Gayk Tags: Molecular and Cellular Pathobiology Source Type: research
Loss of Igf2 Gene Imprinting in Murine Prostate Promotes Widespread Neoplastic Growth
In this study, we created a mouse model with CTCF-binding site mutations at the Igf2-H19 imprint control region that abolishes CTCF insulator activity, resulting in biallelic Igf2 expression that mimics increased levels seen with aging-induced LOI. We found that Igf2 LOI increased the prevalence and severity of prostatic intraepithelial neoplasia (PIN), a premalignant lesion. Engineering Nkx3.1 deficiency into our model increased the frequency of PIN lesions in an additive fashion. Prostates harboring LOI displayed increased MAPK signaling and epithelial proliferation. In human prostate tissue arrays, we documented a posit...
Source: Cancer Research - October 1, 2017 Category: Cancer & Oncology Authors: Nathan A. Damaschke, Bing Yang, Sachin Bhusari, Mele Avilla, Weixiong Zhong, Michael L. Blute, Jr, Wei Huang, David F. Jarrard Tags: Molecular and Cellular Pathobiology Source Type: research
Targeting a Single Alternative Polyadenylation Site Coordinately Blocks Expression of Androgen Receptor mRNA Splice Variants in Prostate Cancer
Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant–specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3. Blocking this signal with morpholino technology or silencing of the polyadenylation f...
Source: Cancer Research - October 1, 2017 Category: Cancer & Oncology Authors: Jamie L. Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel Johnson, Olivia Ondigi, Daniel F. Voytas, Christine Henzler, Scott M. Dehm Tags: Priority Report Source Type: research
New Advances and Challenges of Targeting Cancer Stem Cells
The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20–23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop. The reported advances of CSC research and therapies fostered new c...
Source: Cancer Research - October 1, 2017 Category: Cancer & Oncology Authors: Nurmaa K. Dashzeveg, Rokana Taftaf, Erika K. Ramos, Luke Torre-Healy, Anastasia Chumakova, Daniel J. Silver, Tyler J. Alban, Maksim Sinyuk, Praveena S. Thiagarajan, Awad M. Jarrar, Soumya M. Turaga, Caner Saygin, Erin Mulkearns-Hubert, Masahiro Hitomi, Je Tags: Meeting Report Source Type: research
Roles for Innate Immunity in Combination Immunotherapies
Immunity to infectious agents involves a coordinated response of innate and adaptive immune cells working in concert, with many feed-forward and regulatory interactions between both arms of the immune system. In contrast, many therapeutic strategies to augment immunity against tumors have focused predominantly on stimulation of adaptive immunity. However, a growing appreciation of the potential contributions of innate immune effectors to antitumor immunity, especially in the context of combination immunotherapy, is leading to novel strategies to elicit a more integrated immune response against cancer. Here we review antitu...
Source: Cancer Research - October 1, 2017 Category: Cancer & Oncology Authors: Kelly D. Moynihan, Darrell J. Irvine Tags: Review Source Type: research
Highlights from Recent Cancer Literature
(Source: Cancer Research)
Source: Cancer Research - October 1, 2017 Category: Cancer & Oncology Tags: Breaking Advances Source Type: research
Retraction: CYP1B1 Gene Polymorphisms Have Higher Risk for Endometrial Cancer, and Positive Correlations with Estrogen Receptor {alpha} and Estrogen Receptor {beta} Expressions
(Source: Cancer Research)
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Tags: Retraction Source Type: research
An Essential Role of Maspin in Embryogenesis and Tumor Suppression—Response
(Source: Cancer Research)
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Ming Zhang, Mary J.C. Hendrix, Philip A. Pemberton, Wael A. Sakr, Shijie Sheng Tags: Letter to the Editor Source Type: research
An Essential Role of Maspin in Embryogenesis and Tumor Suppression—Letter
(Source: Cancer Research)
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: James C. Whisstock, Phillip I. Bird Tags: Letter to the Editor Source Type: research
Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers
Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe (P (Source: Cancer Research)
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Vasudha Murlidhar, Rishindra M. Reddy, Shamileh Fouladdel, Lili Zhao, Martin K. Ishikawa, Svetlana Grabauskiene, Zhuo Zhang, Jules Lin, Andrew C. Chang, Philip Carrott, William R. Lynch, Mark B. Orringer, Chandan Kumar-Sinha, Nallasivam Palanisamy, David Tags: Clinical Studies Source Type: research
Mathematical Modeling of Tumor-Tumor Distant Interactions Supports a Systemic Control of Tumor Growth
Interactions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition, and proliferation inhibition) have been proposed, but precise determinants of the phenomenon remain poorly understood. Here, we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day...
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Sebastien Benzekry, Clare Lamont, Dominique Barbolosi, Lynn Hlatky, Philip Hahnfeldt Tags: Integrated Systems and Technologies Source Type: research
Adipose Progenitor Cell Secretion of GM-CSF and MMP9 Promotes a Stromal and Immunological Microenvironment That Supports Breast Cancer Progression
In this study, we identified two proteins that were significantly upregulated in WAT-derived progenitors after coculture with breast cancer: granulocyte macrophage colony-stimulating factor (GM-CSF) and matrix metallopeptidase 9 (MMP9). These proteins were released by WAT progenitors in xenograft and transgenic breast cancer models. GM-CSF was identified as an upstream modulator. Breast cancer–derived GM-CSF induced GM-CSF and MMP9 release from WAT progenitors, and GM-CSF knockdown in breast cancer cells neutralized the protumorigenic activity of WAT progenitors in preclinical models. GM-CSF neutralization in diet-induce...
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Francesca Reggiani, Valentina Labanca, Patrizia Mancuso, Cristina Rabascio, Giovanna Talarico, Stefania Orecchioni, Andrea Manconi, Francesco Bertolini Tags: Microenvironment and Immunology Source Type: research
Proinflammatory CXCL12-CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice
In this study, we provide preclinical proof of concept for the role of a proinflammatory CXCL12–CXCR4/CXCR7 signaling axis in an obesity-driven mouse model of myc-induced prostate cancer. Analysis of the stromal vascular fraction from periprostatic white adipose tissue from obese HiMyc mice at 6 months of age revealed a dramatic increase in mRNAs encoding various chemokines, cytokines, growth factors, and angiogenesis mediators, with CXCL12 among the most significantly upregulated genes. Immunofluorescence staining of ventral prostate tissue from obese HiMyc mice revealed high levels of CXCL12 in the stromal compartment ...
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Achinto Saha, Songyeon Ahn, Jorge Blando, Fei Su, Mikhail G. Kolonin, John DiGiovanni Tags: Microenvironment and Immunology Source Type: research
Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells
Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship with MSCs is not clear. Here, we have isolated from primary human neuroblastoma tumors a population of αFAP- and FSP-1–expressing CAFs that share phenotypic and functional characteristics with bone marrow–derived MSCs (BM-MSC). Analysis of human neuroblastoma tumors also confirmed the presence of αFAP- and FSP-1–positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages. These cells (designated CAF-MSCs) enhanced in vitro neuroblastoma ...
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Lucia Borriello, Rie Nakata, Michael A. Sheard, G. Esteban Fernandez, Richard Sposto, Jemily Malvar, Laurence Blavier, Hiroyuki Shimada, Shahab Asgharzadeh, Robert C. Seeger, Yves A. DeClerck Tags: Microenvironment and Immunology Source Type: research
Kindlin-2 Regulates the Growth of Breast Cancer Tumors by Activating CSF-1-Mediated Macrophage Infiltration
In this study, we show how the integrin-regulatory protein kindlin-2 (FERMT2) promotes metastatic progression of breast cancer through the recruitment and subversion of host macrophages. Kindlin-2 expression was elevated in breast cancer biopsy tissues where its levels correlated with reduced patient survival. On the basis of these observations, we used CRISPR/Cas9 technology to ablate Kindlin-2 expression in human MDA-MB-231 and murine 4T1 breast cancer cells. Kindlin-2 deficiency inhibited invasive and migratory properties in vitro without affecting proliferation rates. However, in vivo tumor outgrowth was inhibited by>8...
Source: Cancer Research - September 14, 2017 Category: Cancer & Oncology Authors: Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Dorota Szpak, Yvonne Parker, Chevaun D. Morrison, Daniel J. Lindner, William P. Schiemann, Edward F. Plow Tags: Microenvironment and Immunology Source Type: research
