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TAM receptors

Wankun Chen, Yajun Xu, Jing Zhong, Huihui Wang, Meilin Weng, Qian Cheng, Qichao Wu, Zhirong Sun, Hui Jiang, Minmin Zhu, Yu Ren, Pingbo Xu, Jiawei Chen, Changhong Miao
Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underlying pathways require to be elucidated. In this study, we detected a positive association between MFHAS1 expression in TAMs and human colorectal cancer (CRC) TNM stage...
October 21, 2016: Oncotarget
Alexandra Sufit, Alisa B Lee-Sherick, Deborah DeRyckere, Manali Rupji, Bhakti Dwivedi, Marileila Varella-Garcia, Angela M Pierce, Jeanne Kowalski, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Amy K Keating, Douglas K Graham
BACKGROUND: MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. METHODS: Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database...
2016: PloS One
Robert I Menzies, Frederick W Tam, Robert J Unwin, Matthew A Bailey
Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function...
October 22, 2016: Kidney International
Jihye Han, Joonbeom Bae, Chang-Yong Choi, Sang-Pil Choi, Hyung-Sik Kang, Eun-Kyeong Jo, Jongsun Park, Young Sik Lee, Hyun-Seuk Moon, Chung-Gyu Park, Myung-Shik Lee, Taehoon Chun
Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation...
October 26, 2016: Autophagy
Magdalena Paolino, Josef M Penninger
The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases...
October 21, 2016: Cancers
Takashi Dejima, Kenjiro Imada, Ario Takeuchi, Masaki Shiota, Jeffrey Leong, Tabitha Tombe, Kevin Tam, Ladan Fazli, Seiji Naito, Martin E Gleave, Christopher J Ong
BACKGROUND: LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO). METHODS: A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy...
October 24, 2016: Prostate
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
October 17, 2016: Immunobiology
Jiang Yue, James F Griffith, Fan Xiao, Lin Shi, Defeng Wang, Jiayun Shen, Priscilla Wong, Edmund K Li, Martin Li, Tena K Li, Tracy Y Zhu, Vivian W Hung, Ling Qin, Lai-Shan Tam
Objective To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods This is a post-hoc analysis of a randomized-controlled trial (NCT01770106). 40 patients were randomized in a 1:1 ratio to receive either subcutaneous denosumab (60mg) once or oral alendronate (70mg) weekly for 6 months. The size of individual bone erosions and the presence and extent of erosion-associated sclerosis (marginal osteosclerosis) were measured in the second metacarpal head of the non-dominant hand at baseline, 3 and 6 months...
October 21, 2016: Arthritis Care & Research
E Fehri, E Ennaifer, R Bel Haj Rhouma, L Guizani-Tabbane, I Guizani, S Boubaker
Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis...
July 2016: Current Research in Translational Medicine
Frank Cackowski, Matthew R Eber, James Rhee, Ann Decker, Kenji Yumoto, Janice E Berry, Eunsohl Lee, Yusuke Shiozawa, Younghun Jung, Julio A Aguirre-Ghiso, Russell S Taichman
Many prostate cancer (PCa) recurrences are thought to be due to reactivation of disseminated tumor cells (DTCs). We previously found a role of the TAM family of receptor tyrosine kinases TYRO3, AXL and MERTK in PCa dormancy regulation. However, the mechanism and contributions of the individual TAM receptors is largely unknown. Knockdown of MERTK, but not AXL or TYRO3 by shRNA in PCa cells induced a decreased ratio of P-Erk1/2 to P-p38, increased expression of p27, NR2F1, SOX2, and NANOG, induced higher levels of histone H3K9me3 and H3K27me3, and induced a G1/G0 arrest, all of which are associated with dormancy...
October 18, 2016: Journal of Cellular Biochemistry
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro Perez-Mancera, Sarah E Coupland, Azzam F Taktak, Thomas Bogenrieder, David A Tuveson, Fiona Campbell, Michael C Schmid, Ainhoa Mielgo
Tumor associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors 1 and 2 (IGF), which activate Insulin/IGF receptors on pancreatic cancer cells...
October 14, 2016: Cancer Research
Anna Malawista, Xiaomei Wang, Mark Trentalange, Heather G Allore, Ruth R Montgomery
The TAM receptors (Tyro3, Axl, and Mer) are a family of homologous receptor-tyrosine kinases that inhibit Toll-like receptor signaling to regulate downstream pathways and restore homeostasis. TAM triple mutant mice (Tyro3(-/-), Axl(-/-), Mer(-/-)) have elevated levels of pro-inflammatory cytokines and are prone to developing lymphoproliferative disorders and autoimmunity. Understanding differential expression of TAM receptors among human subjects is critical to harnessing this pathway for therapeutic interventions...
2016: Macrophage
Michael Boice, Darin Salloum, Frederic Mourcin, Viraj Sanghvi, Rada Amin, Elisa Oricchio, Man Jiang, Anja Mottok, Nicolas Denis-Lagache, Giovanni Ciriello, Wayne Tam, Julie Teruya-Feldstein, Elisa de Stanchina, Wing C Chan, Sami N Malek, Daisuke Ennishi, Renier J Brentjens, Randy D Gascoyne, Michel Cogné, Karin Tarte, Hans-Guido Wendel
The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (TFH) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors...
October 6, 2016: Cell
Baoqing Guo, Adam Tam, Stacey A Santi, Amadeo M Parissenti
BACKGROUND: The roles and mechanisms involved in starvation-induced autophagy in mammalian cells have been extensively studied. However, less is known about the potential role for autophagy as a survival pathway in acquired drug resistance in cancer cells under nutrient-rich conditions. METHODS: We selected MCF-7 breast tumor cells for survival in increasing concentrations of doxorubicin and assessed whether the acquisition of doxorubicin resistance was accompanied by changes in doxorubicin and lysosome localization and the activation of autophagy, as assessed by laser scanning confocal microscopy with or without immunohistochemical approaches...
September 29, 2016: BMC Cancer
Tong Wang, Sally Martin, Tam H Nguyen, Callista B Harper, Rachel S Gormal, Ramon Martínez-Mármol, Shanker Karunanithi, Elizabeth J Coulson, Nick R Glass, Justin J Cooper-White, Bruno van Swinderen, Frédéric A Meunier
Axonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic activity markedly increased the flux of plasma membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured in microfluidic devices, and live Drosophila larval motor neurons...
2016: Nature Communications
Florian Finkernagel, Silke Reinartz, Sonja Lieber, Till Adhikary, Annika Wortmann, Nathalie Hoffmann, Tim Bieringer, Andrea Nist, Thorsten Stiewe, Julia M Jansen, Uwe Wagner, Sabine Müller-Brüsselbach, Rolf Müller
Macrophages occur as resident cells of fetal origin or as infiltrating blood monocyte-derived cells. Despite the critical role of tumor-associated macrophages (TAMs) in tumor progression, the contribution of these developmentally and functionally distinct macrophage subsets and their alteration by the tumor microenvironment are poorly understood. We have addressed this question by comparing TAMs from human ovarian carcinoma ascites, resident peritoneal macrophages (pMPHs) and monocyte-derived macrophages (MDMs)...
September 21, 2016: Oncotarget
Salman Goudarzi, Andrea Rivera, Arthur M Butt, Sassan Hafizi
A key aim of therapy for multiple sclerosis (MS) is to promote the regeneration of oligodendrocytes and remyelination in the central nervous system (CNS). The present study provides evidence that the vitamin K-dependent protein growth arrest specific 6 (Gas6) promotes such repair in in vitro cultures of mouse optic nerve and cerebellum. We first determined expression of Gas6 and TAM (Tyro3, Axl, Mer) receptors in the mouse CNS, with all three TAM receptors increasing in expression through postnatal development, reaching maximal levels in the adult...
October 2016: ASN Neuro
Sènan M d'Almeida, Gilles Kauffenstein, Charlotte Roy, Laetitia Basset, Loukas Papargyris, Daniel Henrion, Véronique Catros, Norbert Ifrah, Philippe Descamps, Anne Croue, Pascale Jeannin, Marc Grégoire, Yves Delneste, Julie Tabiasco
Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor...
July 2016: Oncoimmunology
Paulomi Aldo, Yuan You, Klara Szigeti, Tamas L Horvath, Brett Lindenbach, Gil Mor
PROBLEM: Zika virus (ZIKV) has gained public concern for its association with microcephaly in infants born to ZIKV-infected mothers. To reach the fetus the virus must overcome the defense mechanisms provided by trophoblast cells. Additionally, in the first trimester, the integrity of the placenta is critical for fetal protection as damage to differentiating trophoblast can affect placental formation and function. We sought to investigate the effect of ZIKV infection on trophoblast cells and the factors that might increase the risk for ZIKV infection during pregnancy...
November 2016: American Journal of Reproductive Immunology: AJRI
Leena Hilakivi-Clarke, Anni Wärri, Kerrie B Bouker, Xiyuan Zhang, Katherine L Cook, Lu Jin, Alan Zwart, Nguyen Nguyen, Rong Hu, M Idalia Cruz, Sonia de Assis, Xiao Wang, Jason Xuan, Yue Wang, Bryan Wehrenberg, Robert Clarke
BACKGROUND: Responses to endocrine therapies vary among patients with estrogen receptor (ER+) breast cancer. We studied whether in utero exposure to endocrine-disrupting compounds might explain these variations. METHODS: We describe a novel ER+ breast cancer model to study de novo and acquired tamoxifen (TAM) resistance. Pregnant Sprague Dawley rats were exposed to 0 or 0.1 ppm ethinyl estradiol (EE2), and the response of 9,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors to 15 mg/kg TAM, with (n = 17 tumors in the controls and n = 20 tumors in EE2 offspring) or without 1...
January 2017: Journal of the National Cancer Institute
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