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Oncogene

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https://www.readbyqxmd.com/read/28218905/phosphorylation-mediated-activation-of-ldha-promotes-cancer-cell-invasion-and-tumour-metastasis
#1
L Jin, J Chun, C Pan, G N Alesi, D Li, K R Magliocca, Y Kang, Z G Chen, D M Shin, F R Khuri, J Fan, S Kang
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218904/the-protumorigenic-potential-of-fty720-by-promoting-extramedullary-hematopoiesis-and-mdsc-accumulation
#2
Y Li, T Zhou, Y Wang, C Ning, Z Lv, G Han, J C Morris, E N Taylor, R Wang, H Xiao, C Hou, Y Ma, B Shen, J Feng, R Guo, Y Li, G Chen
FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218903/macrophage-migration-inhibitory-factor-downregulation-a-novel-mechanism-of-resistance-to-anti-angiogenic-therapy
#3
B A Castro, P Flanigan, A Jahangiri, D Hoffman, W Chen, R Kuang, M De Lay, G Yagnik, J R Wagner, S Mascharak, M Sidorov, S Shrivastav, G Kohanbash, H Okada, M K Aghi
Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218902/retinoic-acid-directs-breast-cancer-cell-state-changes-through-regulation-of-tet2-pkc%C3%AE-pathway
#4
M-J Wu, M R Kim, Y-S Chen, J-Y Yang, C-J Chang
The key molecular mechanism governing the cancer cell state (stem cell-like state vs differentiation state) to control the cancer stem cell (CSC) pool remains elusive. This study provides the first evidence showing that all-trans retinoic acid (ATRA) induces the interaction and chromatin recruitment of a novel RARβ-TET2 complex to epigenetically activate a specific cohort of gene targets, including MiR-200c. TET2-activated miR-200c further targets and suppresses PKCζ, a cell polarity protein that has a pivotal role in directing asymmetric division of mammalian stem cells to sustain the stem cell pool...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218901/girdin-maintains-the-stemness-of-glioblastoma-stem-cells
#5
A Natsume, T Kato, S Kinjo, A Enomoto, H Toda, S Shimato, F Ohka, K Motomura, Y Kondo, T Miyata, M Takahashi, T Wakabayashi
No abstract text is available yet for this article.
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28192409/melanocyte-transformation-requires-complete-loss-of-all-pocket-protein-function-via-a-mechanism-that-mitigates-the-need-for-mapk-pathway-activation
#6
I D Tonks, P Mukhopadhyay, W A Schroder, A Sorolla, A W Mould, H Y Handoko, B Ferguson, H K Muller, P Keith, N K Hayward, G J Walker, G F Kay
Deregulation of p16INK4A is a critical event in melanoma susceptibility and progression. It is generally assumed that the major effect of loss of p16 function is mediated through the CDK-cyclin pathway via its influence on the pocket protein (PP) pRb. However, there are also two other PPs, p107 and p130, which, when phosphorylated by CDK-cyclin complexes, play a role in permitting cell progression. Cohorts of mice carrying melanocyte-specific knockouts (KOs) of various combinations of the three PPs were generated...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192408/macrophages-confer-survival-signals-via-ccr1-dependent-translational-mcl-1-induction-in-chronic-lymphocytic-leukemia
#7
M H A van Attekum, S Terpstra, E Slinger, M von Lindern, P D Moerland, A Jongejan, A P Kater, E Eldering
Protective interactions with bystander cells in micro-environmental niches, such as lymph nodes (LNs), contribute to survival and therapy resistance of chronic lymphocytic leukemia (CLL) cells. This is caused by a shift in expression of B-cell lymphoma 2 (BCL-2) family members. Pro-survival proteins B-cell lymphoma-extra large (BCL-XL), BCL-2-related protein A1 (BFL-1) and myeloid leukemia cell differentiation protein 1 (MCL-1) are upregulated by LN-residing T cells through CD40L interaction, presumably via nuclear factor (NF)-κB signaling...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192407/ttf-1-nkx2-1-binds-to-ddb1-and-confers-replication-stress-resistance-to-lung-adenocarcinomas
#8
Z Liu, K Yanagisawa, S Griesing, M Iwai, K Kano, N Hotta, T Kajino, M Suzuki, T Takahashi
TTF-1, also known as NKX2-1, is a transcription factor that has indispensable roles in both lung development and physiology. We and others have reported that TTF-1 frequently exhibits high expression with increased copy number in lung adenocarcinomas, and also has a role as a lineage-survival oncogene through transcriptional activation of crucial target genes including ROR1 and LMO3. In the present study, we employed a global proteomic search for proteins that interact with TTF-1 in order to provide a more comprehensive picture of this still enigmatic lineage-survival oncogene...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192406/ras-erk-signaling-induces-phosphorylation-of-human-tle1-and-downregulates-its-repressor-function
#9
T Zahavi, A Maimon, T Kushnir, R Lange, E Berger, D Kornspan, R Grossman, S Anzi, E Shaulian, R Karni, H Nechushtan, Z Paroush
Signaling mediated by the Ras-extracellular signal-regulated kinase (Erk) pathway often leads to the phosphorylation of transcriptional regulators, thereby modulating their activity and causing concerted changes in gene expression. In Drosophila, the induction of multiple Ras-Erk pathway target genes depends on prior phosphorylation of the general co-repressor Groucho, a modification that downregulates its repressive function. Here, we show that TLE1, one of the four human Groucho orthologs, is similarly phosphorylated in response to Ras-Erk pathway activation, and that this modification attenuates its capacity to repress transcription...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192405/cftr-is-a-tumor-suppressor-gene-in-murine-and-human-intestinal-cancer
#10
B L N Than, J F Linnekamp, T K Starr, D A Largaespada, A Rod, Y Zhang, V Bruner, J Abrahante, A Schumann, T Luczak, J Walter, A Niemczyk, M G O'Sullivan, J P Medema, R J A Fijneman, G A Meijer, E Van den Broek, C A Hodges, P M Scott, L Vermeulen, R T Cormier
No abstract text is available yet for this article.
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192404/isoprenylcysteine-carboxylmethyltransferase-is-critical-for-malignant-transformation-and-tumor-maintenance-by-all-ras-isoforms
#11
H Y Lau, J Tang, P J Casey, M Wang
Despite extensive effort, there has been limited progress in the development of direct RAS inhibitors. Targeting isoprenylcysteine carboxylmethyltransferase (ICMT), a unique enzyme of RAS post-translational modification, represents a promising strategy to inhibit RAS function. However, there lacks direct genetic evidence on the role of ICMT in RAS-driven human cancer initiation and maintenance. Using CRISPR/Cas9 genome editing, we have created Icmt loss-of-function isogenic cell lines for both RAS-transformed human mammary epithelial cells (HME1) and human cancer cell lines MiaPaca-2 and MDA-MB-231 containing naturally occurring mutant KRAS...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192403/a-double-negative-feedback-loop-between-epcam-and-erk-contributes-to-the-regulation-of-epithelial-mesenchymal-transition-in-cancer
#12
N V Sankpal, T P Fleming, P K Sharma, H J Wiedner, W E Gillanders
Epithelial-mesenchymal transition (EMT) is an important biological process that has been implicated in cancer metastasis. Epithelial cell adhesion molecule (EpCAM) is expressed at the basolateral membrane of most normal epithelial cells but is overexpressed in many epithelial cancers. In our studies on the role of EpCAM in cancer biology, we observed that EpCAM expression is decreased in mesenchymal-like primary cancer specimens in vivo and following induction of EMT in cancer cell lines in vitro. Extracellular signal-related kinase (ERK) is a key regulator of EMT...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192402/loss-of-klf4-and-consequential-downregulation-of-smad7-exacerbate-oncogenic-tgf-%C3%AE-signaling-in-and-promote-progression-of-hepatocellular-carcinoma
#13
H Sun, Z Peng, H Tang, D Xie, Z Jia, L Zhong, S Zhao, Z Ma, Y Gao, L Zeng, R Luo, K Xie
Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192401/prima-1-met-induces-mitochondrial-apoptosis-through-activation-of-caspase-2
#14
J Shen, H Vakifahmetoglu, H Stridh, B Zhivotovsky, K G Wiman
No abstract text is available yet for this article.
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192400/oncogenic-signaling-by-kit-tyrosine-kinase-occurs-selectively-on-the-golgi-apparatus-in-gastrointestinal-stromal-tumors
#15
Y Obata, K Horikawa, T Takahashi, Y Akieda, M Tsujimoto, J A Fletcher, H Esumi, T Nishida, R Abe
Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Here, we show that in cancer tissue from primary GIST patients as well as in cell lines, mutant Kit accumulates on the Golgi apparatus, whereas normal Kit localizes to the plasma membrane (PM)...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192399/c-met-mir-130b-axis-as-novel-mechanism-and-biomarker-for-castration-resistance-state-acquisition
#16
A Cannistraci, G Federici, A Addario, A L Di Pace, L Grassi, G Muto, D Collura, M Signore, L De Salvo, S Sentinelli, G Simone, M Costantini, S Nanni, A Farsetti, V Coppola, R De Maria, D Bonci
Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192398/cyclind-cdk4-6-complexes-phosphorylate-cdc25a-and-regulate-its-stability
#17
C Dozier, L Mazzolini, C Cénac, C Froment, O Burlet-Schiltz, A Besson, S Manenti
The phosphatase CDC25A is a key regulator of cell cycle progression by dephosphorylating and activating cyclin-CDK complexes. CDC25A is an unstable protein expressed from G1 until mitosis. CDC25A overexpression, which can be caused by stabilization of the protein, accelerates the G1/S and G2/M transitions, leading to genomic instability and promoting tumorigenesis. Thus, controlling CDC25A protein levels by regulating its stability is a critical mechanism for timing cell cycle progression and to maintain genomic integrity...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28192397/downregulation-of-mir-218-contributes-to-epithelial-mesenchymal-transition-and-tumor-metastasis-in-lung-cancer-by-targeting-slug-zeb2-signaling
#18
Z-M Shi, L Wang, H Shen, C-F Jiang, X Ge, D-M Li, Y-Y Wen, H-R Sun, M-H Pan, W Li, Y-Q Shu, L-Z Liu, S C Peiper, J He, B-H Jiang
Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28166203/lncrna-hulc-triggers-autophagy-via-stabilizing-sirt1-and-attenuates-the-chemosensitivity-of-hcc-cells
#19
H Xiong, Z Ni, J He, S Jiang, X Li, J He, W Gong, L Zheng, S Chen, B Li, N Zhang, X Lyu, G Huang, B Chen, Y Zhang, F He
Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28166202/cgi-99-promotes-breast-cancer-metastasis-via-autocrine-interleukin-6-signaling
#20
C Lin, W Liao, Y Jian, Y Peng, X Zhang, L Ye, Y Cui, B Wang, X Wu, Z Xiong, S Wu, J Li, X Wang, L Song
Metastatic relapse remains largely incurable and a major challenge of clinical management in breast cancer, but the underlying mechanisms are poorly understood. Herein, we report that CGI-99 is overexpressed in breast cancer tissues from patients with metastatic recurrence within 5 years. High CGI-99 significantly predicts poorer 5-year metastasis-free patient survival. We find that CGI-99 increases breast cancer stem cell properties, and potentiates efficient tumor lung colonization and outgrowth in vivo. Furthermore, we demonstrate that CGI-99 activates the autocrine interleukin-6 (IL-6)/STAT3 signaling by increasing the accumulation and activity of RNA polymerase II and p300 cofactor at the proximal promoter of IL-6...
February 6, 2017: Oncogene
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