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L-L Zuo, J Zhang, L-Z Liu, Q Zhou, S-J Du, S-Y Xin, Z-P Ning, J Yang, H-B Yu, W-X Yue, J Wang, F-X Zhu, G-Y Li, J-H Lu
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203...
December 22, 2017: Oncogenesis
Olatz Arrizabalaga, Leire Moreno-Cugnon, Jaione Auzmendi-Iriarte, Paula Aldaz, Inmaculada Ibañez de Cáceres, Laura Garros-Regulez, Veronica Moncho-Amor, Sergio Torres-Bayona, Olga Pernía, Laura Pintado-Berninches, Patricia Carrasco-Ramirez, María Cortes-Sempere, Rocío Rosas, Pilar Sanchez-Gomez, Irune Ruiz, Helena Caren, Steven Pollard, Idoia Garcia, Angel-Ayuso Sacido, Robin Lovell-Badge, Cristobal Belda-Iniesta, Nicolas Sampron, Rosario Perona, Ander Matheu
The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC...
December 14, 2017: Oncogenesis
D Alwyn Dart, Pinar Uysal-Onganer, W G Jiang
PTen loss is one of the most frequent events in prostate cancer both at the initiation stage and during late stage metastatic development. The mouse model of prostate-specific probasin-mediated Pten deletion leads to prostate intraepithelial neoplasia (PIN) leading to adenocarcinoma. Using this model, we analysed the miR and mRNA transcriptome profile of Pten -/- PIN versus wild type age-matched prostate tissues and analysed the effects of Pten loss on miR expression in the early neoplastic process. At the PIN stage, Pten loss significantly changed the expression of over 20 miRNAs and over 4000 genes...
December 14, 2017: Oncogenesis
Petra Vychytilova-Faltejskova, Jana Merhautova, Tana Machackova, Irene Gutierrez-Garcia, José Garcia-Solano, Lenka Radova, Dominika Brchnelova, Katerina Slaba, Marek Svoboda, Jana Halamkova, Regina Demlova, Igor Kiss, Rostislav Vyzula, Pablo Conesa-Zamora, Ondrej Slaby
Growing evidence suggests that microRNAs are involved in the development and progression of colorectal cancer (CRC). In the present study, deregulation and functioning of tumor-suppressive miR-215-5p was evaluated in CRC. In total, 448 tumor tissues and 325 paired adjacent healthy tissues collected from Czech and Spain cohorts of CRC patients have been used for miR-215-5p expression analyses. A series of in vitro experiments have been performed using transient transfection of miR-215-5p mimics into four CRC cell lines to identify specific cellular processes affected by miR-215-5p...
December 4, 2017: Oncogenesis
Takashi Matsumoto, Takeshi Uchiumi, Keisuke Monji, Mikako Yagi, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, Masaki Shiota, Masatoshi Eto, Dongchon Kang
Tumor heterogeneity can be traced back to a small subset of cancer stem cells (CSCs), which can be derived from a single stem cell and show chemoresistance. Recent studies showed that CSCs are sensitive to mitochondrial targeting antibiotics such as doxycycline. However, little is known about how cancer cells undergo sphere formation and how antibiotics inhibit CSC proliferation. Here we show that under sphere-forming assay conditions, prostate cancer cells acquired CSC-like properties: promoted mitochondrial respiratory chain activity, expression of characteristic CSC markers and resistance to anticancer agents...
November 29, 2017: Oncogenesis
Julia Langhans, Lukas Schneele, Nancy Trenkler, Hélène von Bandemer, Lisa Nonnenmacher, Georg Karpel-Massler, Markus D Siegelin, Shaoxia Zhou, Marc-Eric Halatsch, Klaus-Michael Debatin, Mike-Andrew Westhoff
The PI3K/Akt/mTOR signalling network is activated in almost 90% of all glioblastoma, the most common primary brain tumour, which is almost invariably lethal within 15 months of diagnosis. Despite intensive research, modulation of this signalling cascade has so far yielded little therapeutic benefit, suggesting that the role of the PI3K network as a pro-survival factor in glioblastoma and therefore a potential target in combination therapy should be re-evaluated. Therefore, we used two distinct pharmacological inhibitors that block signalling at different points of the cascade, namely, GDC-0941 (Pictilisib), a direct inhibitor of the near apical PI3K, and Rapamycin which blocks the side arm of the network that is regulated by mTOR complex 1...
November 29, 2017: Oncogenesis
Zehua Bian, Jiwei Zhang, Min Li, Yuyang Feng, Surui Yao, Mingxun Song, Xiaowei Qi, Bojian Fei, Yuan Yin, Dong Hua, Zhaohui Huang
Long intergenic non-coding RNA 152 (LINC00152) is a recently identified tumor-promoting long non-coding RNA. However, the biological functions of LINC00152 in colorectal cancer (CRC) remain unclear and require further research. The aim of the present study is to explore the roles of LINC00152 in cellular function and its possible molecular mechanism. In this study, we discovered that LINC00152 was overexpressed in CRC tissues and negatively related to the survival time of CRC patients. Functional analyses revealed that LINC00152 could promote cell proliferation...
November 28, 2017: Oncogenesis
J Chuck Harrell, Thomas M Shroka, Britta M Jacobsen
Among the molecular subtypes of breast cancer are luminal (A or B) estrogen receptor positive (ER+), HER2+, and triple negative (basal-like). In addition to the molecular subtypes, there are 18 histologic breast cancer subtypes classified on appearance, including invasive lobular breast carcinoma (ILC), which are 8-15% of all breast cancers and are largely ER+ tumors. We used a new model of ER+ ILC, called BCK4. To determine the estrogen regulated genes in our ILC model, we examined BCK4 xenograft tumors from mice supplemented with or without estrogen using gene expression arrays...
November 27, 2017: Oncogenesis
H M Jeong, J Han, S H Lee, H-J Park, H J Lee, J-S Choi, Y M Lee, Y-L Choi, Y K Shin, M J Kwon
This corrects the article DOI: 10.1038/oncsis.2017.87.
November 20, 2017: Oncogenesis
P Mathot, M Grandin, G Devailly, F Souaze, V Cahais, S Moran, M Campone, Z Herceg, M Esteller, P Juin, P Mehlen, R Dante
Breast cancer-associated fibroblasts (CAFs) have a crucial role in tumor initiation, metastasis and therapeutic resistance by secreting various growth factors, cytokines, protease and extracellular matrix components. Soluble factors secreted by CAFs are involved in many pathways including inflammation, metabolism, proliferation and epigenetic modulation, suggesting that CAF-dependent reprograming of cancer cells affects a large set of genes. This paracrine signaling has an important role in tumor progression, thus deciphering some of these processes could lead to relevant discoveries with subsequent clinical implications...
October 23, 2017: Oncogenesis
H M Jeong, J Han, S H Lee, H-J Park, H J Lee, J-S Choi, Y M Lee, Y-L Choi, Y K Shin, M J Kwon
Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2), epithelial cell-specific regulators of alternative splicing, are downregulated during the epithelial-mesenchymal transition (EMT). These factors have roles in tumor progression and metastasis in some cancers; however, their expression and function in ovarian cancer (OC) remain unclear. We found that ESRP1 and ESRP2 mRNAs were expressed at higher levels in OC cells than in immortalized ovarian surface epithelial (IOSE) cells, and confirmed their overexpression in OC tissues at the protein level...
October 9, 2017: Oncogenesis
E L Kavanagh, S Lindsay, M Halasz, L C Gubbins, K Weiner-Gorzel, M H Z Guang, A McGoldrick, E Collins, M Henry, A Blanco-Fernández, P O' Gorman, P Fitzpatrick, M J Higgins, P Dowling, A McCann
Triple negative breast cancer (TNBC) is an aggressive subtype with relatively poor clinical outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemoresistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy...
October 9, 2017: Oncogenesis
J Tang, M-N Zhan, Q-Q Yin, C-X Zhou, C-L Wang, L-L Wo, M He, G-Q Chen, Q Zhao
Aberrant activation of nuclear factor-κB (NF-κB) has been observed in a wide range of human cancers and is thought to promote tumorigenesis and metastasis. As a central component of NF-κB pathway, p65 protein level is tightly regulated and could be subjected to proteasome degradation. Here we demonstrated that p65 can bind to HSC70 with four consensus recognition motif in its RHD domain and be constitutively transported to the lysosome membrane to bind with lysosome-associated membrane protein type 2A and degraded within the lysosome in two epithelial cell lines, proposing that p65 can be degraded by chaperone-mediated autophagy (CMA)...
October 9, 2017: Oncogenesis
S-U Woo, T Sangai, A Akcakanat, H Chen, C Wei, F Meric-Bernstam
Deregulation and activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian (or mechanistic) target of rapamycin (mTOR) pathway have a major role in proliferation and cell survival in breast cancer. However, as single agents, mTOR inhibitors have had modest antitumor efficacy. In this study, we evaluated the effects of vertical inhibition of mTOR and Akt in breast cancer cell lines and xenografts. We assessed the effects of mTOR inhibitor rapamycin and Akt inhibitor MK-2206, given as single drugs or in combination, on cell signaling, cell proliferation and apoptosis in a panel of cancer cell lines in vitro...
October 9, 2017: Oncogenesis
G Jin, Y Yang, K Liu, J Zhao, X Chen, H Liu, R Bai, X Li, Y Jiang, X Zhang, J Lu, Z Dong
Tumor microenvironment has a crucial role in cancer development and progression, whereas the mechanism of how it regulates angiogenesis is unclear. In this study, we simulated the colorectal carcinoma microenvironment by conditioned medium (CM) of colorectal carcinoma cell lines (SW620, HT-29, HCT116) supernatant or colorectal carcinoma tissue homogenate supernatant to induce normal endothelial cells (NECs). We found that colorectal carcinoma CM promoted tumor angiogenesis by coercing NECs toward tumor endothelial cells (TECs) with the activation of the JAK/STAT3 signaling pathway...
October 2, 2017: Oncogenesis
G Zhu, Q Qi, J J Havel, Z Li, Y Du, X Zhang, H Fu
PRAS40 has been shown to have a crucial role in the repression of mammalian target of rapamycin (mTOR). Nonetheless, PRAS40 appears to have an oncogenic function in cancer cells. Whether PRAS40 mediates signaling independent of mTOR inhibition in cancer cells remains elusive. Here PRAS40 overexpression in lung adenocarcinoma and cutaneous melanoma was significantly correlated to worse prognosis. And we identified an unexpected role for PRAS40 in the regulation of nuclear factor (NF)-κB signaling. P65, a subunit of the NF-κB transcription factor complex, was confirmed to associate with PRAS40 by glutathione S-transferase co-precipitation...
September 25, 2017: Oncogenesis
Y Gao, Y Yang, F Yuan, J Huang, W Xu, B Mao, Z Yuan, W Bi
Clinical and experimental evidence indicates that macrophages could promote solid-tumor progression and metastasis. However, the mechanisms underlying this process remain unclear. Here we show that yes-associated protein 1 (YAP1), a transcriptional regulator that controls tissue growth and regeneration, has an important role in tumor necrosis factor α (TNF α)-induced breast cancer migration. Mechanistically, macrophage conditioned medium (CM) or TNFα triggers IκB kinases (IKKs)-mediated YAP phosphorylation and activation in breast cancer cells...
September 25, 2017: Oncogenesis
G-L Chen, T Ye, H-L Chen, Z-Y Zhao, W-Q Tang, L-S Wang, J-L Xia
Xanthine dehydrogenase (XDH), a rate-limiting enzyme involved in purine metabolism, has an essential role in inflammatory cascades. Researchers have known for decades that XDH activity is decreased in some cancers, including hepatocellular carcinoma (HCC). However, the role of XDH in cancer pathogenesis has not been fully explored. In this study, we showed that low XDH mRNA levels were correlated with higher tumor stages and poorer prognoses in patients with HCC. Knocking down or inhibiting XDH promoted migration and invasion but not proliferation of HCC cells...
September 25, 2017: Oncogenesis
A Gress, V Ramensky, O V Kalinina
Next-generation sequencing enables simultaneous analysis of hundreds of human genomes associated with a particular phenotype, for example, a disease. These genomes naturally contain a lot of sequence variation that ranges from single-nucleotide variants (SNVs) to large-scale structural rearrangements. In order to establish a functional connection between genotype and disease-associated phenotypes, one needs to distinguish disease drivers from neutral passenger variants. Functional annotation based on experimental assays is feasible only for a limited number of candidate mutations...
September 25, 2017: Oncogenesis
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
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