A5052928717- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Beetle Biology and Toxicology Studies
- Ferroptosis and cancer prognosis
- Immunotherapy and Immune Responses
- Heat shock proteins research
- Phagocytosis and Immune Regulation
- Cancer Mechanisms and Therapy
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Angiogenesis and VEGF in Cancer
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Wnt/β-catenin signaling in development and cancer
- Protein Degradation and Inhibitors
University of Chieti-Pescara
2016-2025
Thomas Jefferson University
2011-2015
Sidney Kimmel Cancer Center
2011-2015
The Wistar Institute
2013
Drexel University
2013
Michigan Center for Translational Pathology
2013
University of Massachusetts Chan Medical School
2010
Mario Negri Sud Foundation
2007
Trop-2 is a calcium signal transducer that drives tumor growth. Anti-Trop-2 antibodies with selective reactivity versus maturation stages allowed to identify two different pools of Trop-2, one localized in the cell membrane and cytoplasm. Of note, membrane-localized/functional was found be differentially associated determinants aggressiveness distinct breast cancer subgroups. These findings candidated states having an impact on progression. We tested this model cancer. A large, consecutive...
Abstract The molecular mechanisms underlying metastatic dissemination are still not completely understood. We have recently shown that β1 integrin-dependent cell adhesion to fibronectin and signaling is affected by a transmembrane molecule, Trop-2, which frequently upregulated in human carcinomas. Here, we report Trop-2 promotes of prostate cancer cells vivo abundantly expressed metastasis from cancer. also show here migration on fibronectin, phenomenon dependent integrins. Mechanistically,...
β-catenin plays an important role as regulatory hub in several cellular processes including cell adhesion, metabolism, and epithelial mesenchymal transition. This is mainly achieved by its dual structural component of cadherin-based adherens junctions, a key nuclear effector the Wnt pathway. For this role, different classes proteins are differentially regulated via dependent mechanisms. Here, we applied liquid chromatography-mass spectrometry (LC-MS/MS) approach to identify modulated after...
// Marco Trerotola 1,2,6 , Kirat K. Ganguly 1,2 Ladan Fazli 3 Carmine Fedele Huimin Lu Anindita Dutta Qin Liu 1,4 Tiziana De Angelis Luke W. Riddell Natalia A. Riobo 5 Martin E. Gleave Amina Zoubeidi Richard G. Pestell 2 Dario C. Altieri and Lucia R. Languino 1 Prostate Cancer Discovery Development Program, Thomas Jefferson University, Philadelphia, PA, USA Department of Biology, Sidney Kimmel Center, The Vancouver Centre, University British Columbia, Vancouver, Canada 4 Tumor...
Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 T88. Molecular modeling indicated this induces profound rearrangement structure, which suggested deep impact on biological function. No was detected normal human tissues, whereas most tumors showed cleavage, including skin, ovary, colon,...
Abstract Endoplasmic reticulum (ER) retention of misfolded glycoproteins is mediated by the ER‐localized eukaryotic glycoprotein secretion checkpoint, UDP‐glucose glucosyl‐transferase (UGGT). The enzyme recognizes a and flags it for ER re‐glucosylating one its N ‐linked glycans. In background congenital mutation in secreted gene, UGGT‐mediated can cause rare disease, even if mutant retains activity (“responsive mutant”). Using confocal laser scanning microscopy, we investigated here...
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene, leading to chronic, unresolved inflammation of airways due uncontrolled recruitment polymorphonuclear leukocytes (PMNs). Evidence indicates that loss‐of‐function, addition promoting pro‐inflammatory phenotype, associated with an increased risk developing cancer, suggesting can exert tumor‐suppressor functions. Three‐dimensional (3D) vitro culture models, such as lung...
Abstract A chimeric CYCLIN D1-TROP2 mRNA was isolated from human ovarian and mammary cancer cells. The shown to be a potent oncogene as it transforms naïve, primary cells in vitro induces aggressive tumor growth vivo cooperation with activated RAS. Silencing of the inhibits breast expressed by large fraction gastrointestinal, ovarian, endometrial tumors analyzed. It is most frequently detected intestinal cell aneuploid cancers coexpressed RAS oncogenes, consistent cooperative transforming...
Abstract Trop‐2 is a transmembrane glycoprotein upregulated in several human carcinomas, including prostate cancer (PrCa). has been suggested to regulate cell–cell adhesion, given its high homology with the other member of Trop family, Trop‐1/EpCAM, and ability bind tight junction proteins claudin‐1 claudin‐7. However, role for cell adhesion extracellular matrix never postulated. Here, we show first time that expression PrCa cells correlates their aggressiveness. Using either shRNA‐mediated...
The growing understanding of the molecular mechanisms underlying epithelial-to-mesenchymal transition (EMT) may represent a potential source clinical markers. Despite EMT drivers have not yet emerged as candidate markers in setting, their association with established improve specificity and sensitivity. Mass spectrometry-based platforms allow analyzing multiple samples for expression markers, help to diagnose diseases or monitor treatment efficiently. This review highlights proteomic...
Inhibition of AKT is a key target area for personalized cancer medicine. However, predictive markers response to inhibitors are lacking. Correspondingly, the AKT-dependent chain command tumor growth, which will mediate therapeutic responses, remains unclear.Proteomic profiling was utilized identify nodal hubs Trop-2 growth-driving network. Kinase-specific were used dissect Trop-2-dependent from Trop-2-independent pathways. In vitro assays, in vivo preclinical models, and case series primary...
We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2–driven progression colon cancer. However, the mechanism action and pathological impact in metastatic diffusion remain unexplored. Through searches for molecular determinants cancer metastasis, we identified TROP2 as unique up-regulation across independent metastasis models. Overexpression wild-type KM12SM human cells increased liver rates vivo immunosuppressed mice. Metastatic growth was...
Abstract Next-generation Trop-2–targeted therapy against advanced cancers is hampered by expression of Trop-2 in normal tissues. We discovered that undergoes proteolytic activation ADAM10 cancer cells, leading to the exposure a previously inaccessible protein groove flanked two N-glycosylation sites. designed recognition strategy for this region, drive selective vulnerability patients. Most undiscriminating anti–Trop-2 mAbs recognize single immunodominant epitope. Hence, we removed it...
// Valeria Relli 1 , Marco Trerotola 1, 2 Emanuela Guerra and Saverio Alberti 3 Unit of Cancer Pathology, CeSI-MeT, University "G. d'Annunzio", Chieti, Italy Department Medical, Oral Biotechnological Sciences, Biomedical Dentistry, Morphological Functional Imaging, Messina, Correspondence to: Alberti, email: salberti@unime.it Keywords: non-small cell lung cancer; adenocarcinomas; squamous carcinomas; prognostic determinants; survival curves Received: August 31, 2018 Accepted: September 26,...
Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed gluco- and/or lipotoxic conditions and those islets from T2D donors. We assessed whether metformin could relieve the β-cell stress induced by pro-inflammatory cytokines (which mediate damage 1 diabetes, T1D) investigated underlying mechanisms using shotgun proteomics. Human were 50 U/mL interleukin-1β plus 1000 interferon-γ for 48 h, with or without 2.4 µg/mL metformin. Glucose-stimulated...