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Scientific Reports
Autophagy
Oncogene
Differential role of MyD88 and Mal/TIRAP in TLR2-mediated gastric tumourigenesis.
Kennedy CL, Najdovska M, Tye H, McLeod L, Yu L, Jarnicki A, Bhathal PS, Putoczki T, Ernst M, Jenkins BJ.
Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash
University, Clayton, Victoria, Australia.
Signalling by the toll-like receptor (TLR) family of pathogen recognition receptors has emerged as a key
molecular component in the pathogenesis of an increasing number of inflammatory-related cancers, among
which gastric cancer rates as the second most lethal cancer world-wide. The myeloid differentiation factor
88 (MyD88) adapter molecule has a critical role in mediating innate immune signalling by members of the
TLR and interleukin (IL)-1 families, and has been associated with either pro- or antitumourigenic responses in
various cancer models. However, little is known about the in vivo role of MyD88 adapter-like (Mal)/TIRdomain containing adapter protein (TIRAP), which is restricted to facilitating TLR4 and TLR2 signalling. To
interrogate the role of these innate immune signalling components in gastric tumourigenesis, here we have
employed the spontaneous gastric cancer gp130F/F mouse model, in which TLR2 promotes the growth of
gastric tumours. Genetic ablation of Myd88 in gp130F/F mice suppressed tumourigenesis and was associated
with increased apoptosis and reduced proliferation in the gastric tumour epithelium, comparable to that
observed previously upon deletion of Tlr2 in gp130F/F mice. By contrast, the tumour burden in gp130F/F:Mal-/mice was equivalent to their gp130F/F littermates. At the molecular level, suppressed tumourigenesis in
gp130F/F:Myd88-/- mice correlated with reduced expression and activation of TLR2-regulated
protumourigenic genes and signalling pathways, respectively. Consistent with the previously defined nonessential role for TLR2 in gastric tumour inflammation, the extent of inflammatory cell infiltrates in gastric
tumours from gp130F/F:Mal-/- and gp130F/F:Myd88-/- mice remained unaltered compared with gp130F/F mice.
Collectively, our data reveal a differential, but inflammation-independent, requirement for Mal and MyD88
during TLR2-promoted gastric tumourigenesis.
Oncogene
Melanoma metastasis: new concepts and evolving paradigms.
Damsky WE, Theodosakis N, Bosenberg M.
Source
1] Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA [2]
Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA.
Abstract
Melanoma progression is typically depicted as a linear and stepwise process in which metastasis
occurs relatively late in disease progression. Significant evidence suggests that in a subset of
melanomas, progression is much more complex and less linear in nature. Epidemiologic and
experimental observations in melanoma metastasis are reviewed here and are incorporated into
a comprehensive model for melanoma metastasis, which takes into account the varied natural
history of melanoma formation and progression.
Small-molecule inhibition of CBP/catenin interactions eliminates
drug-resistant clones in acute lymphoblastic leukemia.
Gang EJ, Hsieh YT, Pham J, Zhao Y, Nguyen C, Huantes S, Park E, Naing
K, Klemm L, Swaminathan S, Conway EM,Pelus LM, Crispino
J, Mullighan CG, McMillan M, Müschen M, Kahn M, Kim YM.
Children's Hospital Los Angeles, Division of Hematology and Oncology,
Department of Pediatrics, University of Southern California, Keck
School of Medicine, Los Angeles, CA, USA
The ribosomal protein S26 regulates p53 activity in response to DNA
damage.
Cui D, Li L, Lou H, Sun H, Ngai SM, Shao G, Tang J.
1] State Key Laboratory of Agrobiotechnology, China Agricultural
University, Beijing, China [2] Department of Basic Veterinary Medicine,
College of Veterinary Medicine, China Agricultural University, Beijing,
China.
H-Ras-driven tumoral maintenance is sustained through caveolin-1dependent alterations in calcium signaling.
Rimessi A, Marchi S, Patergnani S, Pinton P.
Deparment of Morphology, Surgery and Experimental Medicine,
Section of General Pathology, Interdisciplinary Center for the Study of
Inflammation (ICSI), Laboratory for Technologies of Advanced
Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Osteopontin signaling upregulates cyclooxygenase-2 expression in
tumor-associated macrophages leading to enhanced angiogenesis
and melanoma growth via α9β1 integrin.
Kale S, Raja R, Thorat D, Soundararajan G, Patil TV, Kundu GC.
Laboratory of Tumor Biology, Angiogenesis and Nanomedicine
Research, National Center for Cell Science, Pune, India.
Oncogene
Irradiation-induced angiogenesis is associated with an MMP-9-miR494-syndecan-1 regulatory loop in medulloblastoma cells.
Asuthkar S, Velpula KK, Nalla AK, Gogineni VR, Gondi CS, Rao JS.
Department of Cancer Biology and Pharmacology, University of Illinois
College of Medicine at Peoria, Peoria, IL, USA.
Failure to downregulate the BAF53a subunit of the SWI/SNF
chromatin remodeling complex contributes to the differentiation
block in rhabdomyosarcoma.
Taulli R, Foglizzo V, Morena D, Coda DM, Ala U, Bersani F, Maestro
N, Ponzetto C.
1] Department of Oncology, University of Turin School of Medicine,
Turin, Italy [2] CERMS, Center for Experimental Research and Medical
Studies, Turin, Italy.
A chemical biology approach identifies AMPK as a modulator of
melanomaoncogene MITF.
Borgdorff V, Rix U, Winter GE, Gridling M, Müller AC, Breitwieser
FP, Wagner C, Colinge J, Bennett KL, Superti-Furga G, Wagner SN.
1] Division of Immunology, Allergy and Infectious Diseases,
Department of Dermatology, Medical University of Vienna, Vienna,
Austria [2] CeMM Research Center for Molecular Medicine of the
Austrian Academy of Sciences, Vienna, Austria.
MicroRNA-29c functions as a tumor suppressor by direct targeting
oncogenic SIRT1 in hepatocellular carcinoma.
Bae HJ, Noh JH, Kim JK, Eun JW, Jung KH, Kim MG, Chang YG, Shen
Q, Kim SJ, Park WS, Lee JY, Nam SW.
1] Laboratory of Oncogenomics, Department of Pathology, College of
Medicine, Catholic University of Korea, Seoul, Republic of Korea [2]
Functional RNomics Research Center, Catholic University of Korea,
Seoul, Republic of Korea.
miR-30 as a tumor suppressor connects EGF/Src signal to ERG and
EMT.
Kao CJ, Martiniez A, Shi XB, Yang J, Evans CP, Dobi A, Devere White
RW, Kung HJ.
Source
Department of Biochemistry and Molecular Medicine, University of
California-Davis, Davis, CA, USA.
Cancer-associated fibroblasts and M2-polarized macrophages
synergize during prostate carcinoma progression.
Comito G, Giannoni E, Segura CP, Barcellos-de-Souza P, Raspollini
MR, Baroni G, Lanciotti M, Serni S, Chiarugi P.
Source
Department of Experimental and Clinical Biomedical Sciences,
University of Florence, Florence, Italy.
EGFRvIII stimulates glioma growth and invasion through PKAdependent serine phosphorylation of Dock180.
Feng H, Hu B, Vuori K, Sarkaria JN, Furnari FB, Cavenee WK, Cheng SY.
Source
1] Department of Neurology, Northwestern Brain Tumor Institute,
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
[2] Center for Genetic Medicine, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA [3] The Robert H Lurie
Comprehensive Cancer Center, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA [4] Stem Cell Research Center,
Renji Hospital, School of Medicine, Shanghai Jiao Tong University,
Shanghai, China.
Oncogene
Hypoxia-driven osteopontin contributes to breast tumor growth
through modulation of HIF1α-mediated VEGF-dependent
angiogenesis.
Raja R, Kale S, Thorat D, Soundararajan G, Lohite K, Mane A, Karnik
S, Kundu GC.
Source
Laboratory of Tumor Biology, Angiogenesis and Nanomedicine
Research, National Center for Cell Science, Pune, India.
Differential regulation of proteasome functionality in
reproductive vs. somatic tissues of Drosophila during aging
or oxidative stress
Eleni N. Tsakiri, Gerasimos P. Sykiotis, Issidora S. Papassideri,
Vassilis G. Gorgoulis, Dirk Bohmann, and Ioannis P. Trougakos
Source
FASEB J June 2013 27:2407-2420; published ahead of print March 1, 2013,
doi:10.1096/fj.12-221408
Low dystrophin levels increase survival and improve
muscle pathology and function in dystrophin/utrophin
double-knockout mice
Maaike van Putten, Margriet Hulsker, Courtney Young, Vishna D. Nadarajah,
Hans Heemskerk, Louise van der Weerd, Peter A. C. 't Hoen, Gert-Jan B. van
Ommen, and Annemieke M. Aartsma-Rus
Source
FASEB J June 2013 27:2484-2495; published ahead of print March 4, 2013,
doi:10.1096/fj.12-224170
Interleukin-10 promoter variants predict HPV-positive
tumors and survival of squamous cell carcinoma of the
oropharynx
Lei Jin, Erich M. Sturgis, Xiaolin Cao, Xicheng Song, Taufiq Salahuddin, Qingyi
Wei, and Guojun Li
Source
FASEB J June 2013 27:2496-2503; published ahead of print February 21, 2013,
doi:10.1096/fj.12-226803
The hydrolase DDAH2 enhances pancreatic insulin
secretion by transcriptional regulation of secretagogin
through a Sirt1-dependent mechanism in mice
Kazuhiro Hasegawa, Shu Wakino, Masumi Kimoto, Hitoshi Minakuchi, Keiko
Fujimura, Koji Hosoya, Motoaki Komatsu,
Yuka Kaneko, Takeshi Kanda, Hirobumi Tokuyama, Koichi Hayashi,
and Hiroshi Itoh
Source
FASEB J June 2013 27:2301-2315; published ahead of print February 21,
2013, doi:10.1096/fj.12-226092
Early methyl donor deficiency produces severe gastritis in
mothers and offspring through N-homocysteinylation of
cytoskeleton proteins, cellular stress, and inflammation
Carine Bossenmeyer-Pourié, Grégory Pourié, Violette Koziel,
Deborah Helle, Elise Jeannesson, Jean-Louis Guéant,
and Bernard Beck
Source
FASEB J June 2013 27:2185-2197; published ahead of print February 11, 2013,
doi:10.1096/fj.12-224642
Intracellular signaling in ER stress-induced autophagy in
skeletal muscle cells
Luca Madaro, Valeria Marrocco, Silvia Carnio, Marco Sandri,
and Marina Bouché
Source
FASEB J May 2013 27:1990-2000; published ahead of print February 6, 2013,
doi:10.1096/fj.12-215475
Up-regulation of sarcoplasmic reticulum Ca2+ uptake leads
to cardiac hypertrophy, contractile dysfunction and early
mortality in mice deficient in CASQ2
Anuradha Kalyanasundaram, Véronique A. Lacombe, Andriy E. Belevych,
Lucia Brunello, Cynthia A. Carnes, Paul M.L. Janssen,
Bjørn C. Knollmann, Muthu Periasamy, and Sandor Gyørke
Source
Cardiovasc Res (2013) 98(2): 297-306 first published online November 6,
2012 doi:10.1093/cvr/cvs334
Extracellular matrix protein CCN1 regulates
cardiomyocyte apoptosis in mice with stress-induced
cardiac injury
Pei-Ling Hsu, Bor-Chyuan Su, Qian-Yu Kuok, and Fan-E Mo
Source
Cardiovasc Res (2013) 98(1): 64-72 first published online January 16,
2013 doi:10.1093/cvr/cvt001
Over-expression of calpastatin aggravates cardiotoxicity
induced by doxorubicin
Yanpeng Wang, Dong Zheng, Meng Wei, Jian Ma, Yong Yu,
Ruizhen Chen, James C. Lacefield, Huaxi Xu, and Tianqing Peng
Source
Cardiovasc Res (2013) 98(3): 381-390 first published online March 1,
2013 doi:10.1093/cvr/cvt048
Editor's choice: Protective role of vascular smooth muscle
cell PPARγ in angiotensin II-induced vascular disease
Chiara Marchesi, Asia Rehman, Yohann Rautureau, Daniel A. Kasal, Marie
Briet, Avshalom Leibowitz, Stefania M.C. Simeone,
Talin Ebrahimian, Mario F. Neves, Stefan Offermanns, Frank J. Gonzalez,
Pierre Paradis, and Ernesto L. Schiffrin
Source
Cardiovasc Res (2013) 97(3): 562-570 first published online December 17,
2012 doi:10.1093/cvr/cvs362
AICAR inhibits PPARγ during monocyte differentiation to
attenuate inflammatory responses to atherogenic lipids
Dmitry Namgaladze, Marina Kemmerer, Andreas von Knethen,
and Bernhard Brüne
Source
Cardiovasc Res (2013) 98(3): 479-487 first published online March 25, 2013
doi:10.1093/cvr/cvt073
Extracellular HSP60 induces inflammation through
activating and up-regulating TLRs in cardiomyocytes
Jing Tian, Xin Guo, Xue-Mei Liu, Li Liu, Qi-Fang Weng, Shu-Juan Dong, Anne A.
Knowlton, Wen-Jun Yuan, and Li Lin
Source
Cardiovasc Res (2013) 98(3): 391-401 first published online February 27, 2013
doi:10.1093/cvr/cvt047
Hypoxia-induced autophagy in endothelial cells: a double-edged sword
in the progression of infantile haemangioma?
Gang Chen, Wei Zhang, Yin-Ping Li, Jian-Gang Ren, Ning Xu, Hui Liu, Feng-Qin Wang, Zhi-Jun Sun,
Jun Jia, and Yi-Fang Zhao
Abstract
Aims The aim of this study was to investigate the precise role of hypoxia-induced autophagy in endothelial
cells, and whether it contributes to the distinctive progression of infantile haemangioma (IH).
Methods and results The endothelial cells (EOMA and HUVECs) were cultured under hypoxic conditions for
indicated times (0–72 h). The results showed that short exposure of the endothelial cells to hypoxia
resulted in increased cell survival and proliferation, accompanied by occurrence of autophagy. Prolonged
hypoxia-induced autophagy, correlating with increased cell death, was also detected afterwards.
Correspondingly, autophagy inhibition prevented the enhanced cell survival and proliferation capacity,
advanced the occurrence of cell-death in early hypoxic stage, and meanwhile attenuated the ability of
prolonged hypoxia in cell-death induction. Moreover, our data demonstrated that the functional
transformation of hypoxia-induced autophagy, pro-survival to pro-death, was rigorously regulated by the
switch between hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR)
pathways. Importantly, we also revealed the activation levels of HIF-1α and mTOR, as well as the autophagy
status during the progression of IH.
Conclusion This study unmasks the functional switch between HIF-1α and mTOR in regulating hypoxiainduced autophagy in endothelial cells and, more importantly, indicates its potential role in the progression
of IH.
p53 Protein Isoforms: Key Regulators in the Front Line
of Pathogen Infections?
Olivier Terrier, Jean-Christophe Bourdon, Manuel Rosa-Calatrava
Source
published 04 Apr 2013 | info:doi/10.1371/journal.ppat.1003246
Early Apoptosis of Macrophages Modulated by Injection
of Yersinia pestis YopK Promotes Progression of Primary
Pneumonic Plague
Kristen N. Peters, Miqdad O. Dhariwala, Jennifer M. Hughes Hanks,
Charles R. Brown, Deborah M. Anderson
Source
published 25 Apr 2013 | info:doi/10.1371/journal.ppat.1003324
The JAK-STAT Transcriptional Regulator, STAT-5,
Activates the ATM DNA Damage Pathway to Induce HPV
31 Genome Amplification upon Epithelial
Differentiation
Shiyuan Hong, Laimonis A. Laimins
Source
published 04 Apr 2013 | info:doi/10.1371/journal.ppat.1003295
IL-1β Production through the NLRP3 Inflammasome by
Hepatic Macrophages Links Hepatitis C Virus Infection
with Liver Inflammation and Disease
Amina A. Negash, Hilario J. Ramos, Nanette Crochet, Daryl T. Y. Lau,
Brian Doehle, Neven Papic, Don A. Delker, Juandy Jo, Antonio Bertoletti,
Curt H. Hagedorn, Michael Gale Jr
Source
published 25 Apr 2013 | info:doi/10.1371/journal.ppat.1003330
The Serine Phosphatase SerB of Porphyromonas
gingivalis Suppresses IL-8 Production by
Dephosphorylation of NF-κB RelA/p65
Hiroki Takeuchi, Takanori Hirano, Sarah E. Whitmore, Ichijiro Morisaki,
Atsuo Amano, Richard J. Lamont
Source
published 18 Apr 2013 | info:doi/10.1371/journal.ppat.1003326
Cell Death Control: The Interplay of Apoptosis and
Autophagy in the Pathogenicity of Sclerotinia
sclerotiorum
Mehdi Kabbage, Brett Williams, Martin B. Dickman
Source
published 11 Apr 2013 | info:doi/10.1371/journal.ppat.1003287