Lysophosphatidic acid promotes survival of T lymphoma cells by altering apoptosis and glucose metabolism

AbstractLysophosphatidic acid (LPA) is a bioactive lipid, which plays an indispensable role in various physiological and pathological processes. Moreover, an elevated level of LPA has been observed in malignancies of different origins and implicated in their progression via modulation of proliferation, apoptosis, invasion and metastasis. Interestingly, few recent reports suggest a pivotal role of LPA-modulated metabolism in oncogenesis of ovarian cancer. However, little is understood regarding the role of LPA in the development and progression of T cell malignancies, which are considered as one of the most challenging neoplasms for clinical management. Additionally, mechanisms underlying the LPA-dependent modulation of glucose metabolism in T cell lymphoma are also not known. Therefore, the present study was undertaken to explore the role of LPA-altered apoptosis and glucose metabolism on the survival of T lymphoma cells. Observations of this investigation suggest that LPA supports survival of T lymphoma cells via altering apoptosis and glucose metabolism through changing the level of reactive species, namely nitric oxide and reactive oxygen species along with expression of various survival and glucose metabolism regulatory molecules, including hypoxia-inducible factor 1-alpha, p53, Bcl2, and glucose transporter 3, hexokinase II, pyruvate kinase muscle isozyme 2, monocarboxylate transporter 1, pyruvate dehydrogenase kinase 1. Taken together ‚ the results of the present ...
Source: Apoptosis - Category: Molecular Biology Source Type: research

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Publication date: Available online 3 January 2020Source: Seminars in Cancer BiologyAuthor(s): Kelly Olino, Tristen Park, Ntia AhujaAbstractAdvances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1–4 merkel cell carcinoma5, urological cancers6–8, non-small cell lung cancer9–11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Objective All-trans-N-(4-hydroxyphenyl)retinamide or fenretinide (4-HPR) acts by reactive oxygen species (ROS) and dihydroceramides (DHCers). In early-phase clinical trials 4-HPR has achieved complete responses in T-cell lymphomas (TCL) and neuroblastoma (NB) and signals of activity in ovarian cancer (OV). We defined the activity of 4-HPR metabolites in N-(4-methoxyphenyl)retinamide (MPR), 4-oxo-N-(4-hydroxyphenyl)retinamide (oxoHPR), and the 4-HPR isomer 13-cis-fenretinide (cis-HPR) in NB, OV, and TCL cell lines cultured in physiological hypoxia. Methods We compared the effect of 4-HPR, cis-HPR, oxoHPR, and MPR on cy...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: PRECLINICAL REPORTS Source Type: research
Discussion:The aim of our study was to reveal the genomic landscape of Chinese AITL. The cohort collection was unbiased, the patients' features were in concordance with previous reports that the disease of AITL is mostly found in the elderly (>60) and shows male predominance. Most cases were EBV-positive. Similar to prior studies, somatic mutations in TET2, RHOA, IDH2, and DNMT3A were found at varying frequencies sequentially of 80%, 60%, 40% and 30% in AITL. Co-occurring mutations of TET2/RHOA were found in 50%. RHOA G17V mutations were predominant mutations while we detected three rare sites in AITL including RHOA C16...
Source: Blood - Category: Hematology Authors: Tags: 621. Lymphoma-Genetic/Epigenetic Biology Source Type: research
mTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1–8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)–mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell–dependent fashion. However, typical rapamycin inhi...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
The paralogous C-terminal binding proteins (collectively CtBP) 1 and 2 are evolutionarily conserved transcriptional co-regulators which demonstrate oncogene-like properties such as allowing for the progression of EMT and cellular invasion/migration, and supporting cellular survival through suppression of tumor suppressors (PTEN, p16, E-cadherin, BRCA-1) and pro-apoptotic genes (Bik, Puma, Noxa). Overexpression of CtBP is found in colon, ovarian, breast, and prostate cancers, and often correlates with loss of the tumor suppressors ARF and APC and with poorer prognosis for the patient. CtBP is also an emerging cancer drug ta...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of diseases characterized by clonal expansion of malignant T-cells in the skin. In the course of our quest to screen and identify a potent, selective anti-proliferative drug for CTCL, we discovered that caffeic acid benzyl ester (CABE), a natural component of edible plant species found in high concentrations in propolis, showed increased potency for CTCL (IC50 4 μM) in vitro compared to other tumor types such as melanoma (IC50 25 μM), glioma (IC50 25 μM), multiple myeloma (MM) (IC50 70 μM), head and neck squamous cell carcinoma (HNSCC) (IC50 25 μM), o...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research
SCCOHT is a rare but deadly type of ovarian cancer. It mainly affects young women with the median age about 28 years. Although often diagnosed at an early stage, the prognosis of SCCOHT is nonetheless dismal with a 2-year survival less than 35% due to lack of effective treatments. Unlike common malignancies, the genome of SCCOHT is minimally disturbed. Recently, we and others have discovered inactivating mutations of SMARCA4, the ATPase of the SWI/SNF chromatin remodeling complex, in the majority of SCCOHT along with loss of SMARCA4 protein. Interestingly, SMARCA2, the alternative ATPase of the SWI/SNF complex is also inac...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research
Introduction: Early-phase clinical trials of fenretinide (4-HPR, a synthetic retinoid) have demonstrated durable complete responses in T-cell lymphoma (TCL), neuroblastoma (NB), and signals of activity in ovarian cancer (OV). Cytotoxic mechanisms of 4-HPR include increase of reactive oxygen species (ROS) and dihydroceramides (DHCs). Major 4-HPR metabolites are N-(4-methoxyphenyl)retinamide (MPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (oxo-HPR). MPR is more abundant in human plasma; oxo-HPR is present in lower concentrations. We assessed the relative cytotoxicity and increase of ROS and DHCs at equimolar concentrations of ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research
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