Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations
Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome (“secretome”), including reduced levels of anti-angiogenic factors, elevated l...
Source: Molecular Oncology - August 11, 2015 Category: Cancer & Oncology Authors: M.M. Koczorowska, S. Tholen, F. Bucher, L. Lutz, J.M. Kizhakkedathu, O. De Wever, U. Wellner, M.L. Biniossek, A. Stahl, S. Lassmann, O. Schilling Source Type: research
Fibroblast Activation Protein−α, a Stromal Cell Surface Protease, Shapes Key Features of Cancer Associated Fibroblasts Through Proteome and Degradome Alterations
Cancer-associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome (“secretome”), including reduced levels of anti-angiogenic factors, elevated l...
Source: Molecular Oncology - August 11, 2015 Category: Cancer & Oncology Authors: M.M. Koczorowska, S. Tholen, F. Bucher, L. Lutz, J.M. Kizhakkedathu, O. De Wever, U. Wellner, M.L. Biniossek, A. Stahl, S. Lassmann, O. Schilling Source Type: research
4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer
Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either mani...
Source: Molecular Oncology - August 6, 2015 Category: Cancer & Oncology Authors: Tommaso De Marchi, Ning Qing Liu, Cristoph Stingl, Mieke A. Timmermans, Marcel Smid, Maxime P. Look, Mila Tjoa, Rene B.H. Braakman, Mark Opdam, Sabine C. Linn, Fred C.G.J. Sweep, Paul N. Span, Mike Kliffen, Theo M. Luider, John A. Foekens, John W.M. Marte Source Type: research
Determination of Cell Uptake Pathways for Tumor Inhibitor Lysyl Oxidase Propeptide
The lysyl oxidase propeptide (LOX-PP) is derived from pro-lysyl oxidase (Pro-LOX) by extracellular biosynthetic proteolysis. LOX-PP inhibits breast and prostate cancer xenograft tumor growth and has tumor suppressor activity. Although, several intracellular targets and molecular mechanisms of action of LOX-PP have been identified, LOX-PP uptake pathways have not been reported. Here we demonstrate that the major uptake pathway for recombinant LOX-PP (rLOX-PP) is PI3K-dependent macropinocytosis in PWR-1E, PC3, SCC9, MDA-MB-231 cell lines. (Source: Molecular Oncology)
Source: Molecular Oncology - August 5, 2015 Category: Cancer & Oncology Authors: Gokhan Baris Ozdener, Manish V. Bais, Philip C. Trackman Source Type: research
CARF (Collaborator of ARF) Overexpression in p53-Deficient Cells Promotes Carcinogenesis
Collaborator of ARF (CARF), initially identified as a binding partner of ARF (Alternate Reading Frame), has been shown to activate ARF-p53 pathway by multiple ways including stabilization of ARF and p53 tumor suppressor proteins, and transcriptional repression of a p53 antagonist, HDM2. Level of CARF expression was shown to determine fate of cells. Whereas its knockdown caused apoptosis, its over- and super-expressions caused senescence and increase in malignant properties of cancer cells, respectively, and were closely linked to increase and decrease in p53 activity. (Source: Molecular Oncology)
Source: Molecular Oncology - August 3, 2015 Category: Cancer & Oncology Authors: Rajkumar S. Kalra, Caroline C. Cheung, Anupama Chaudhary, Jay Prakash, Sunil C. Kaul, Renu Wadhwa Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - July 31, 2015 Category: Cancer & Oncology Source Type: research
Genotyping Concordance in DNA Extracted from Formalin-Fixed Paraffin Embedded (FFPE) Breast Tumor and Whole Blood for Pharmacogenetic Analyses
Cancer pharmacogenetic studies have used archival tumor samples as a DNA source when germline DNA was unavailable. Genotyping DNA extracted from formalin-fixed paraffin embedded tumors (FFPE-T) may be inaccurate compared to that from normal leukocytes due to FFPE storage, tumor genetic aberrations, and/or insufficient DNA extraction. Our objective was to assess the extent and source of genotyping inaccuracy from FFPE-T DNA and demonstrate analytical validity of FFPE-T genotyping of candidate single nucleotide polymorphisms (SNPs) for pharmacogenetic analyses. (Source: Molecular Oncology)
Source: Molecular Oncology - July 28, 2015 Category: Cancer & Oncology Authors: Daniel L. Hertz, Kelley M. Kidwell, Jacklyn N. Thibert, Christina Gersch, Meredith M. Regan, Todd C. Skaar, N.Lynn Henry, Daniel F. Hayes, Catherine H. Van Poznak, James M. Rae Source Type: research
PEA3 transcription factors are downstream effectors of Met signaling involved in migration and invasiveness of Met-addicted tumor cells
Various solid tumors including lung or gastric carcinomas display aberrant activation of the Met receptor which correlates with aggressive phenotypes and poor prognosis. Although downstream signaling of Met is well described, its integration at the transcriptional level is poorly understood. We demonstrate here that in cancer cells harboring met gene amplification, inhibition of Met activity with tyrosine kinase inhibitors or specific siRNA drastically decreased expression of ETV1, ETV4 and ETV5, three transcription factors constituting the PEA3 subgroup of the ETS family, while expression of the other members of the famil...
Source: Molecular Oncology - July 15, 2015 Category: Cancer & Oncology Authors: Zoulika Kherrouche, Didier Monte, Elisabeth Werkmeister, Luc Stoven, Yvan De Launoit, Alexis B. Cortot, David Tulasne, Anne Chotteau-Lelievre Source Type: research
ERBB3 is required for tumor promotion in a mouse model of skin carcinogenesis
The epidermal growth factor receptor (EGFR) plays a key role in skin inflammation, wound healing, and carcinogenesis. Less is known about the functions of the structurally related receptor ERBB3 (HER3) in the skin. We assessed the requirement of ERBB3 for skin homeostasis, wound healing, and tumorigenesis by crossing mice carrying a conditional Erbb3 allele with animals expressing cre under the control of the keratin 5 promoter. Erbb3del mice, lacking ERBB3 specifically in keratinocytes, showed no obvious abnormalities. (Source: Molecular Oncology)
Source: Molecular Oncology - July 3, 2015 Category: Cancer & Oncology Authors: Maik Dahlhoff, Matthias Schäfer, Sukalp Muzumdar, Christian Rose, Marlon R. Schneider Source Type: research
Ubiquitin Specific Protease 4 Positively Regulates the WNT/β-catenin Signaling in Colorectal Cancer
β-catenin is a key signal transducer in the canonical WNT pathway and is negatively regulated by ubiquitin-dependent proteolysis. Through screening of various deubiquitinating enzymes (DUBs), we identified ubiquitin specific protease 4 (USP4) as a candidate for β-catenin-specific DUB. The effects of USP4 overexpression or knockdown suggested that USP4 positively controls the stability of β-catenin and enhances β-catenin-regulated transcription. Domain mapping results revealed that the C-terminal catalytic domain is responsible for β-catenin binding and nuclear transport. (Source: Molecular Oncology)
Source: Molecular Oncology - July 3, 2015 Category: Cancer & Oncology Authors: Sun-Il Yun, Hyeon Ho Kim, Jung Hwan Yoon, Won Sang Park, Myong-Joon Hahn, Hee Cheol Kim, Chin Ha Chung, Kyeong Kyu Kim Source Type: research
ERBB3 is required for tumor promotion in a mouse model of skin carcinogenesis
The epidermal growth factor receptor (EGFR) plays a key role in skin inflammation, wound healing, and carcinogenesis. Less is known about the functions of the structurally related receptor ERBB3 (HER3) in the skin. We assessed the requirement of ERBB3 for skin homeostasis, wound healing, and tumorigenesis by crossing mice carrying a conditional Erbb3 allele with animals expressing cre under the control of the keratin 5 promoter. Erbb3del mice, lacking ERBB3 specifically in keratinocytes, showed no obvious abnormalities. (Source: Molecular Oncology)
Source: Molecular Oncology - July 3, 2015 Category: Cancer & Oncology Authors: Maik Dahlhoff, Matthias Schäfer, Sukalp Muzumdar, Christian Rose, Marlon R. Schneider Source Type: research
Hepatocellular Carcinoma: Where There Is Unmet Need
Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor most commonly associated with underlying chronic liver disease, especially hepatitis. It is a growing problem in the United States and worldwide. There are two potential ways to prevent HCC. Primary prevention which is based on vaccination or secondary prevention involving agents that slows down carcinogenesis. Several pathways have been thought to play a role in the development of HCC; specifically, those involving vascular endothelial growth factor (VEGF)-mediated angiogenesis, WNT, phosphatidylinositol 3-kinase (PI3K) / AKT / mammalian target of rapamyc...
Source: Molecular Oncology - June 24, 2015 Category: Cancer & Oncology Authors: Manojkumar Bupathi, Ahmed Kaseb, Funda Meric-Bernstam, Aung Naing Source Type: research
5-Fluorouracil preferentially sensitizes mutant KRAS non-small cell lung carcinoma cells to TRAIL-induced apoptosis
Mutations in the KRAS gene are very common in non–small cell lung cancer (NSCLC), but effective therapies targeting KRAS have yet to be developed. Interest in tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a potent inducer of cell death, has increased following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and in xenograft models. However, results from clinical trials of TRAIL-based therapy are disappointingly modest at best and many have demonstrated a lack of therapeutic benefit. (Source: Molecular Oncology)
Source: Molecular Oncology - June 19, 2015 Category: Cancer & Oncology Authors: Haizhen Wang, Tao Yang, Xiangwei Wu Source Type: research
5 Fluorouracil Preferentially Sensitizes Mutant KRAS Non-Small Cell Lung Carcinoma Cells to TRAIL-Induced Apoptosis
Mutations in the KRAS gene are very common in non–small cell lung cancer (NSCLC), but effective therapies targeting KRAS have yet to be developed. Interest in tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a potent inducer of cell death, has increased following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and in xenograft models. However, results from clinical trials of TRAIL-based therapy are disappointingly modest at best and many have demonstrated a lack of therapeutic benefit. (Source: Molecular Oncology)
Source: Molecular Oncology - June 19, 2015 Category: Cancer & Oncology Authors: Haizhen Wang, Tao Yang, Xiangwei Wu Source Type: research
Guadecitabine (SGI-110) priming sensitizes hepatocellular carcinoma cells to oxaliplatin
Promoter DNA hypermethylation is an important biomarker of hepatocellular carcinoma (HCC), supporting the potential utility of demethylating agents in this disease. Guadecitabine (SGI-110) is a second-generation hypomethylating agent formulated as a dinucleotide of decitabine and deoxyguanosine that yields longer half-life and more extended decitabine exposure than decitabine IV infusion. Here we performed preclinical evaluation of SGI-110 in HCC models to guide the design of a phase I/II clinical trial. (Source: Molecular Oncology)
Source: Molecular Oncology - June 15, 2015 Category: Cancer & Oncology Authors: Yuting Kuang, Anthony El-Khoueiry, Pietro Taverna, Mats Ljungman, Nouri Neamati Source Type: research
