Antonio Amelio

Antonio Amelio
Moffitt Cancer Center · Department of Tumor Biology

Ph.D.

About

54
Publications
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Introduction
Adaptive stress signaling networks directly influence tumor development and progression. These pathways mediate responses that allow cancer cells to cope with both tumor cell-intrinsic and cell-extrinsic insults and develop acquired resistance to therapeutic interventions. This is mediated in part by constant oncogenic rewiring at the transcriptional level by integration of extracellular cues that promote cell survival and malignant transformation. My lab applies an interdisciplinary approach to understand the mechanisms underlying the development and progression of oral, head, and neck cancers. To this end, we use bioinformatics, animal models, and molecular genetic analyses combined with novel optical reporter tools to investigate adaptive response signaling in these malignancies.

Publications

Publications (54)
Article
Full-text available
Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswered: 1. Does LH2 catalyze the hydroxylation of all t...
Article
Full-text available
Over 70% of oropharyngeal head and neck squamous cell carcinoma (HNSC) cases in the United States are positive for human papillomavirus (HPV) yet biomarkers for stratifying oropharyngeal HNSC patient risk are limited. We used immunogenomics to identify differentially expressed genes in immune cells of HPV(+) and HPV(−) squamous carcinomas. Candidat...
Article
Full-text available
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. Patients often present with locally advanced disease and a staggering 50% chance of relapse following treatment. Aberrant activation of adaptive response signaling pathways, such as the cAMP/PKA pathway, induce...
Article
Full-text available
Bioluminescence imaging with luciferase–luciferin pairs is a well-established technique for visualizing biological processes across tissues and whole organisms. Applications at the microscale, by contrast, have been hindered by a lack of detection platforms and easily resolved probes. We addressed this limitation by combining bioluminescence with p...
Preprint
Purpose Human papillomavirus-associated (HPV ⁺ ) head and neck squamous cell carcinoma (HNSCC) is the fastest rising cancer in North America. There is significant interest in treatment de-escalation for these patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved...
Preprint
Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswered: 1, Does LH2 catalyze the hydroxylation of all t...
Article
Full-text available
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. HNSCC patient prognosis is closely related to the occurrence of tumor metastases, and collagen within the tumor microenvironment (TME) plays a key role in this process. Lysyl hydroxylase 2 (LH2), encoded by the...
Article
Objectives Mucoepidermoid carcinoma (MEC) is the most common type of salivary gland malignancy. Advanced or high-grade MECs are refractory to chemotherapy, often leading to tumor recurrence/metastasis and abysmal ~35% 5-year survival. Causal links have been established between Epithelial Growth Factor Receptor (EGFR) activation and poor outcome. He...
Article
Full-text available
Aging drives progressive loss of the ability of tissues to recover from stress, partly through loss of somatic stem cell function and increased senescent burden. We demonstrate that bone marrow‐derived mesenchymal stem cells (BM‐MSCs) rapidly senescence and become dysfunctional in culture. Injection of BM‐MSCs from young mice prolonged life span an...
Article
Full-text available
Bioluminescent imaging (BLI) has emerged as a popular in vivo tracking modality in bone regeneration studies stemming from its clear advantages: non-invasive, real-time, and inexpensive. We recently adopted bioluminescence resonance energy transfer (BRET) principle to improve BLI cell tracking and generated the brightest bioluminescent signal known...
Article
Full-text available
Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor, displaying aggressive behavior with frequent recurrence and metastasis. Little information exists regarding the impact of clinicopathological parameters and adjuvant radiotherapy (aRT) on ACC disease specific (DSS) and overall survival (OS). We extracted demographic, treatment, and surv...
Article
Full-text available
Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by a transcriptional coactivator fusion composed of cyclic AMP-regulated transcriptional coactivator 1 (CRTC1) and mastermind-like 2 (MAML2). The mechanisms by which the chimeric CRTC1/MAML2 (C1/M2) oncoprotein rewires gene expression programs that p...
Conference Paper
p> Introduction: The presence of the t(11;19) chromosomal translocation and its CRTC1-MAML2 (C1/M2) fusion product occurs frequently in salivary mucoepidermoid carcinoma (MEC) and has been correlated with a favorable prognosis. Recently, whole-exome sequencing studies found genomic alterations in MEC to be infrequent, which supports the role of C1/...
Preprint
Full-text available
Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by the transcriptional co-activator fusion CRTC1-MAML2. The mechanisms by which the chimeric CRTC1-MAML2 oncoprotein rewires gene expression programs that promote tumorigenesis remain poorly understood. Here, we show that CRTC1-MAML2 induces transcri...
Article
Full-text available
Light-inducible optogenetic systems offer precise spatiotemporal control over a myriad of biologic processes. Unfortunately, current systems are inherently limited by their dependence on external light sources for their activation. Further, the utility of Laser/LED-based illumination strategies are often constrained by the need for invasive surgica...
Article
Full-text available
The incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to inv...
Article
Background Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor, comprising less than 1% of head and neck neoplasms. Adjuvant radiotherapy (aRT) is suggested for late-stage disease (stage III or IV); however, recent evidence suggests that it may be associated with improved survival even for early-stage disease. Moreover, the prognostic sig...
Article
Full-text available
Drug resistance to anti-cancer agents is a major concern regarding the successful treatment of malignant tumors. Recent studies have suggested that acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies such as cetuximab are in part caused by genetic alterations in patients with oral squamous cell carcinoma (OSCC). However, t...
Conference Paper
Mucoepidermoid carcinoma (MEC) is the most common type of malignant salivary gland tumor. MECs frequently exhibit a recurrent t(11;19)(q21;p13) chromosomal translocation that fuses the transcriptional coactivators CRTC1 (CREB-Regulated Transcription Coactivator 1; C1) and MAML2 (Mastermind-Like 2; M2). Though many C1/M2-positive tumors are easily r...
Article
Full-text available
Elucidating receptor occupancy (RO) of monoclonal antibodies (mAbs) is a crucial step in characterizing the therapeutic efficacy of mAbs. However, the in vivo assessment of RO, particularly within peripheral tissues, is greatly limited by current technologies. In the present study, we developed a bioluminescence resonance energy transfer (BRET)-bas...
Article
Tumor progression is a complex process involving extracellular matrix (ECM) remodeling and stiffening. However, the mechanisms that govern these processes and their roles in tumor progression are still poorly understood. In this study, we performed bioinformatics, immunohistochemical, and biochemical analyses to examine if collagen cross-linking is...
Article
Adaptive stress signaling networks directly influence tumor development and progression. These pathways mediate responses that allow cancer cells to cope with both tumor cell-intrinsic and cell-extrinsic insults and develop acquired resistance to therapeutic interventions. This is mediated in part by constant oncogenic rewiring at the transcription...
Article
Objective: The aim of this study was to perform a systematic analysis of the nicotinamide adenine dinucleotide phosphate (NAD[P])-dependent steroid dehydrogenase-like (NSDHL) gene in cases of oral verruciform xanthoma (VX) and to test for the presence of mutations associated with congenital hemidysplasia with ichthyosiform nevus and limb defects (...
Article
The rate of HPV-induced head and neck squamous cell carcinoma (HNSCC) is steadily increasing and implicated in approximately 60% of all oropharyngeal carcinomas. The advent of whole genome, transcriptome, and proteome analyses have aided in identifying altered signaling pathways in HPV-induced HNSCCs, however, additional tools such as mouse models...
Article
Fluorescent proteins are widely used to study molecular and cellular events, yet this traditionally relies on delivery of excitation light, which can trigger autofluorescence, photoxicity, and photobleaching, impairing their use . Accordingly, chemiluminescent light sources such as those generated by luciferases have emerged, as they do not require...
Article
Full-text available
We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as...
Article
We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as...
Article
Pheochromocytomas (PCC) and paragangliomas (PGL) are tumors of the autonomic nervous system; 25% are metastatic or locally aggressive. Characterization of the inherited basis of disease has identified a variety of underlying germline mutations; however, understanding of somatic alterations remains limited. As part of The Cancer Genome Atlas, we per...
Article
Full-text available
The LKB1 tumor suppressor gene is frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Loss of LKB1 promotes cancer progression and influences therapeutic responses in preclinical studies; however, specific targeted therapies for lung cancer with LKB1 inactivation are currently unavailable. Here, we have identified a long nonco...
Article
Cyclooxygenase-2 (COX-2) directs the synthesis of prostaglandins important for mitogenic signaling. Here we report that COX-2 is a transcriptional target of the CREB co-activator CRTC1. In addition, we detected a correlation between the LKB1-null status and presence of 72/74 kDa glycosylated COX-2, but not inactive hypoglycosylated COX-2 in fresh l...
Article
Metabolic reprogramming is a hallmark of cancer. MYC oncoproteins control many aspects of this response, by inducing the expression of genes involved in mitochondrial biogenesis, glycolysis, glutaminolysis and amino acid transport. This coordinated response allows cancer cells to meet the demands for macromolecules and energy necessary to sustain t...
Article
Endometrial cancer is the most common gynecologic malignancy and the fourth most common malignancy in women. For most patients in whom the disease is confined to the uterus, treatment results in successful remission; however, there are no curative treatments for tumors that have progressed beyond the uterus. The serine/threonine kinase LKB1 has bee...
Article
Full-text available
Fluorescent proteins are widely used to study molecular and cellular events, yet this traditionally relies on delivery of excitation light, which can trigger autofluorescence, photoxicity, and photobleaching, impairing their use in vivo. Accordingly, chemiluminescent light sources such as those generated by luciferases have emerged, as they do not...
Article
Malignant cells exhibit aerobic glycolysis (the Warburg effect) and become dependent on de novo lipogenesis, which sustains rapid proliferation and resistance to cellular stress. The nuclear receptor liver-X-receptor (LXR) directly regulates expression of key glycolytic and lipogenic genes. To disrupt these oncogenic metabolism pathways, we designe...
Article
Full-text available
Background: Cyclooxygenase-2 (COX-2) directs the synthesis of prostaglandins including PGE-2 linking inflammation with mitogenic signaling. COX-2 is also an anticancer target, however, treatment strategies have been limited by unreliable expression assays and by inconsistent tumor responses to COX-2 inhibition. Methods: We analyzed the TCGA and...
Article
Full-text available
The RNA-binding protein Tristetraprolin (TTP, ZFP36) functions as a tumor suppressor that impairs the development and disables the maintenance of MYC-driven lymphoma. In addition, other human cancers expressed reduced levels of TTP, suggesting that it may function as a tumor suppressor in several malignancies. To identify genes that may be associat...
Article
Full-text available
Chimeric oncoproteins created by chromosomal translocations are among the most common genetic mutations associated with tumorigenesis. Malignant mucoepidermoid salivary gland tumors, as well as a growing number of solid epithelial-derived tumors, can arise from a recurrent t (11, 19)(q21;p13.1) translocation that generates an unusual chimeric cAMP...
Article
During the stress response to intense exercise, the sympathetic nervous system (SNS) induces rapid catabolism of energy reserves through the release of catecholamines and subsequent activation of protein kinase A (PKA). Paradoxically, chronic administration of sympathomimetic drugs (β-agonists) leads to anabolic adaptations in skeletal muscle, sugg...
Article
Full-text available
Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1, and that elevated MCT1 levels are manifest in premalignant and neoplastic Eµ-Myc transgenic B cells and in human malignancies with MYC or MYCN inv...
Article
Metabolic reprogramming is a hallmark of cancer. MYC oncoproteins orchestrate the control of many aspects of metabolism, including mitochondrial biogenesis, glycolysis and glutaminolysis. This response allows the highly proliferative cancer cell to meet the increased demands for macromolecules and energy. Here we report that MYC promotes anabolism...
Article
Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Oncogenesis is a complex, multi-factorial process of cellular transformation that leads to the development of many types of cancers. The factors that contribute to this process reprogram normal cellular functions, including metabolic pathways, and allow uncontrolled cell grow...
Article
Full-text available
Cocaine addiction is characterized by a gradual loss of control over drug use, but the molecular mechanisms regulating vulnerability to this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR-212 decreases responsiveness to the m...
Article
Full-text available
HIV-1 gene expression requires both viral and cellular factors to control and coordinate transcription. While the viral factor Tat is known for its transcriptional transactivator properties, we present evidence for an unexpected function of Tat in viral splicing regulation. We used a series of HIV-1 reporter minigenes to demonstrate that Tat’s role...
Article
Full-text available
The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here w...
Article
Full-text available
Signal transduction pathways often use a transcriptional component to mediate adaptive cellular responses. Coactivator proteins function prominently in these pathways as the conduit to the basic transcriptional machinery. Here we present a high-throughput cell-based screening strategy, termed the “coactivator trap,” to study the functional interact...
Article
Full-text available
A previous study demonstrated that the latency-associated transcript (LAT) promoter and the LAT enhancer/reactivation critical region (rcr) are enriched in acetyl histone H3 (K9, K14) during herpes simplex virus type 1 (HSV-1) latency, whereas all lytic genes analyzed (ICP0, UL54, ICP4, and DNA polymerase) are not (N. J. Kubat, R. K. Tran, P. McAna...
Article
Full-text available
Only the latency-associated transcript (LAT) of the herpes simplex virus type 1 (HSV-1) genome is transcribed during latency, while the lytic genes are suppressed, possibly by LAT antisense mechanisms and/or chromatin modifications. In the present study, latently infected dorsal root ganglia were explanted to assess both relative levels of LAT and...
Article
Full-text available
During herpes simplex virus type 1 (HSV-1) latency, only one region of the viral genome is actively transcribed: the region encoding the latency-associated transcript (LAT). A previous study demonstrated that during latency the LAT promoter is hyperacetylated at histone H3 (K9, K14) relative to lytic genes examined. In the present study, we examine...

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