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Shomereeta Roy, Souvick Roy, Madhabananda Kar, Shweta Thakur, Yusuf Akhter, Amit Kumar, Francesco Delogu, Swatishree Padhi, Arka Saha, Birendranath Banerjee
TRF2 is a telomere binding protein, a component of the shelterin complex that plays a major role in maintaining the integrity of the genome. TRF2 is over-expressed in a number of human cancers including Head and Neck cancer and might play a key role in tumor initiation and development. p38 MAPK signaling pathway is strongly activated in response to various environmental and cellular stresses and thus overexpressed in most of the Head and Neck cancer cases. In this study, we investigated potential interactions of TRF2 with p38 in HNSCC cells and patient samples...
July 9, 2018: Oncogenesis
Ramadevi Subramani, Fernando A Camacho, Carly Ivy Levin, Kristina Flores, Alexa Clift, Adriana Galvez, Mauricio Terres, Servando Rivera, Sai Navana Kolli, Joshua Dodderer, Megan Miranda, Alejandro Rodriguez, Diego A Pedroza, Animesh Chatterjee, Rajkumar Lakshmanaswamy
IGF-1R signaling controls various vital cellular functions and this signaling is deregulated in many cancers, including pancreatic cancer. Several efforts have mainly focused on inhibiting the IGF-1R signaling cascade. The outcomes of these focused preclinical studies have been positive, whereas clinical trials of IGF-1R inhibitors in pancreatic cancer have failed, raising the questions about this therapeutic approach. This necessitates a better understanding of the role of IGF-1R signaling in pancreatic cancer...
July 6, 2018: Oncogenesis
Olga Ostrovsky, Ania Hava Grushchenko-Polaq, Katia Beider, Margarita Mayorov, Jonathan Canaani, Avichai Shimoni, Israel Vlodavsky, Arnon Nagler
Heparanase is an endo-β-glucuronidase that specifically cleaves the saccharide chains of heparan sulfate (HS) proteoglycans and releases HS-bound cytokines, chemokines, and bioactive growth-promoting factors. Heparanase plays an important role in the nucleus as part of an active chromatin complex. Our previous studies revealed that rs4693608 correlates with heparanase levels and increased risk of acute and extensive chronic graft vs. host disease (GVHD). Discrepancy between recipient and donor in this SNP significantly affected the risk of acute GVHD...
June 29, 2018: Oncogenesis
Kevin K Chang, Changhwan Yoon, Brendan C Yi, William D Tap, M Celeste Simon, Sam S Yoon
Sarcomas are malignant tumors derived from mesenchymal tissues and may harbor a subset of cells with cancer stem-like cell (CSC) properties. Platelet-derived growth factor receptors α and β (PDGFR-α/β) play an important role in the maintenance of mesenchymal stem cells. Here we examine the role of PDGFR-α/β in sarcoma CSCs. PDGFR-α/β activity and the effects of PDGFR-α/β inhibition were examined in 3 human sarcoma cell lines using in vitro assays and mouse xenograft models. In all three cell lines, PDGFR-α/β activity was significantly higher in cells grown as spheroids (to enrich for CSCs) and in cells sorted for CD133 expression (a marker of sarcoma CSCs)...
June 19, 2018: Oncogenesis
Imerio Angriman, Lucrezia Furian, Melania Scarpa, Matteo Fassan, Susan Morgan, Andrea Porzionato, Andromachi Kotsafti, Luca Saadeh, Cristina Silvestre, Raffaele De Caro, Amedeo Carraro, Umberto Tedeschi, Romeo Bardini, Paolo Rigotti, Massimo Rugge, Carlo Castoro, Ignazio Castagliuolo, Marco Scarpa
BACKGROUND: Ulcerative colitis patients and transplant recipients are at risk for colorectal cancer. Here, we show that immunosuppressive regimens for kidney transplants are associated with the progression of ulcerative colitis-related carcinogenesis. METHODS: We describe the case of a patient diagnosed with colorectal cancer in ulcerative colitis while on immunosuppressive therapy for a kidney transplant. The immunological microenvironment of the cancer and its mutational status were analyzed, and a mouse colon cancer model was created to replicate the unique clinical conditions...
June 19, 2018: Oncogenesis
Jianmin Sun, Tine Thingholm, Peter Højrup, Lars Rönnstrand
In order to investigate the molecular mechanisms by which the oncogenic mutant KIT/D816V causes transformation of cells, we investigated proteins that selectively bind KIT/D816V, but not wild-type KIT, as potential mediators of transformation. By mass spectrometry several proteins were identified, among them a previously uncharacterized protein denoted XKR5 (XK-related protein 5), which is related to the X Kell blood group proteins. We could demonstrate that interaction between XKR5 and KIT/D816V leads to phosphorylation of XKR5 at Tyr 369, Tyr487, and Tyr 543...
June 18, 2018: Oncogenesis
Uilst Bat-Erdene, Eric Quan, Kelvin Chan, Brianna-Marie Lee, Wejdan Matook, Ki-Young Lee, Jesusa L Rosales
A proliferation-inducing ligand (APRIL), which induces survival and migration signals and tumor growth, is commonly observed in breast cancer tissues but is not often expressed in breast cancer cells themselves. Here, we examined whether breast cancer cells induce APRIL secretion from neutrophils, which are frequently recruited into the breast tumor microenvironment. We found that breast cancer cells do stimulate neutrophils to secrete APRIL through their glycosaminoglycans. Breast cancer cells depleted of heparan sulfate or chondroitin sulfate glycosaminoglycans lose their ability to induce APRIL secretion from neutrophils, and heparan sulfate and chondroitin sulfate can induce secretion that is comparable to that of breast cancer cell-induced secretion...
June 15, 2018: Oncogenesis
Jiwei Guo, Yan Wu, Jing Du, Lijuan Yang, Weiwei Chen, Kaikai Gong, Juanjuan Dai, Shuang Miao, Dan Jin, Sichuan Xi
The roles of aberrantly regulated autophagy in human malignancy and the mechanisms that initiate and sustain the repression of autophagy in carcinogenesis are less well defined. Activation of the oncogene UBE2C and repression of autophagy are concurrently underlying the initiation, progression, and metastasis of lung cancer and exploration of essential association of UBE2C with autophagy will confer more options in searching novel molecular therapeutic targets in lung cancer. Here we report that aberrant activation of UBE2C in lung tumors from patients associates with adverse prognosis and enhances cell proliferation, clonogenicity, and invasive growth of NSCLC...
June 13, 2018: Oncogenesis
Jianqing Liang, Jie Fan, Manna Wang, Zubiao Niu, Zhengrong Zhang, Long Yuan, Yanhong Tai, Zhaolie Chen, Santai Song, Xiaoning Wang, Xiaoqing Liu, Hongyan Huang, Qiang Sun
Cell-in-cell (CIC) structures, characterized by enclosure of one or more cells within another cell, were extensively documented in human cancers. Although elevated CIC formation was found in cancers with CDKN2A inactivation, a causal link between them remains to be established. We reported here that inhibiting CDKN2A expression effectively promoted homotypic CIC formation, whereas ectopic overexpression of p16INK4a or p14ARF, two proteins encoded by CDKN2A gene, significantly suppressed CIC formation in MCF7 cells...
June 5, 2018: Oncogenesis
Furong Wang, Bin Li, Yucai Wei, Yang Zhao, Li Wang, Peng Zhang, Jinwei Yang, Wenting He, Hao Chen, Zuoyi Jiao, Yumin Li
Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutively expressed programmed cell death 1 (PD1) and accumulated in advanced-stage gastric cancer (GC). These PD1+ tumor-associated macrophages (TAMs) exhibited an M2-like surface profile, with a significant increase in the expression of CD206, IL-10, and CCL1, and a clear decrease in the expression of MHC class II, CD64, and IL-12 and the ability to phagocytose ovalbumin...
May 25, 2018: Oncogenesis
Aki Pui-Wah Tse, Karen Man-Fong Sze, Queenie Tsung-Kwan Shea, Elley Yung-Tuen Chiu, Felice Ho-Ching Tsang, David Kung-Chun Chiu, Misty Shuo Zhang, Derek Lee, Iris Ming-Jing Xu, Cerise Yuen-Ki Chan, Hui-Yu Koh, Chun-Ming Wong, Yong-Ping Zheng, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Hepatocellular carcinoma (HCC), accounting for 90% of primary liver cancer, is a lethal malignancy that is tightly associated with chronic hepatitis B virus (HBV) infection. HBV encodes a viral onco-protein, transactivator protein X (HBx), which interacts with proteins of hepatocytes to promote oncogenesis. Our current study focused on the interaction of HBx with a transcription factor, hypoxia-inducible factor-1α (HIF-1α), which is stabilized by low O2 condition (hypoxia) and is found to be frequently overexpressed in HCC intra-tumorally due to poor blood perfusion...
May 25, 2018: Oncogenesis
Giulia Diluvio, Francesca Del Gaudio, Maria Valeria Giuli, Giulia Franciosa, Eugenia Giuliani, Rocco Palermo, Zein Mersini Besharat, Maria Gemma Pignataro, Alessandra Vacca, Giulia d'Amati, Marella Maroder, Claudio Talora, Carlo Capalbo, Diana Bellavia, Saula Checquolo
Notch dysregulation has been implicated in numerous tumors, including triple-negative breast cancer (TNBC), which is the breast cancer subtype with the worst clinical outcome. However, the importance of individual receptors in TNBC and their specific mechanism of action remain to be elucidated, even if recent findings suggested a specific role of activated-Notch3 in a subset of TNBCs. Epidermal growth factor receptor (EGFR) is overexpressed in TNBCs but the use of anti-EGFR agents (including tyrosine kinase inhibitors, TKIs) has not been approved for the treatment of these patients, as clinical trials have shown disappointing results...
May 25, 2018: Oncogenesis
Rashi Kalra, Ella Bhagyaraj, Drishti Tiwari, Ravikanth Nanduri, Anuja P Chacko, Monika Jain, Sahil Mahajan, Neeraj Khatri, Pawan Gupta
Early stage prostate cancers are dependent on androgens for their growth and survival and androgen withdrawal causes them to regress. Progressive prostate cancers eventually acquire androgen independence rendering anti-androgen therapy ineffective. However, the factors leading to this have not been adequately addressed. This study shows that AIRE finds differential expression in androgen-dependent and -independent prostate cancer cells. AIRE expression is more in androgen-independent cells due to its regulation by transcription factor Elk-1...
May 25, 2018: Oncogenesis
Pierre-Antoine Bissey, Jacqueline H Law, Jeff P Bruce, Wei Shi, Aline Renoult, Melvin L K Chua, Kenneth W Yip, Fei-Fei Liu
Despite the improvement in locoregional control of nasopharyngeal carcinoma (NPC), distant metastasis (DM), and chemoresistance persist as major causes of mortality. This study identified a novel role for miR-449b, an overexpressed gene in a validated four-miRNA signature for NPC DM, leading to chemoresistance via the direct targeting of transforming growth factor beta-induced (TGFBI). In vitro shRNA-mediated downregulation of TGFBI induced phosphorylation of PTEN and AKT, increasing cisplatin resistance. Conversely, the overexpression of TGFBI sensitized the NPC cells to cisplatin...
May 22, 2018: Oncogenesis
Rajkumar S Kalra, Anupama Chaudhary, A-Rum Yoon, Priyanshu Bhargava, Amr Omar, Sukant Garg, Chae-Ok Yun, Sunil C Kaul, Renu Wadhwa
CARF (Collaborator of ARF)/CDKN2AIP was discovered as a novel ARF-binding protein. It has been established as an essential cell survival, p53-, and cell proliferation-regulatory protein. Although a moderate upregulation of CARF caused growth arrest and senescence, its excessively enriched levels were shown to facilitate aggressive proliferation and malignant transformation of cancer cells. Here, we examined the relevance of CARF levels in clinical tumors and found its amplification (both at gene and transcript levels) in a variety of invasive and metastatic malignancies...
May 11, 2018: Oncogenesis
Wei Chen, Kyung L Kang, Abdullah Alshaikh, Saaket Varma, Yi-Ling Lin, Ki-Hyuk Shin, Reuben Kim, Cun-Yu Wang, No-Hee Park, Katharina Walentin, Kai M Schmidt-Ott, Mo K Kang
Grainyhead-Like 2 (GRHL2) is an epithelial-specific transcription factor that regulates epithelial morphogenesis and differentiation. Prior studies suggested inverse regulation between GRHL2 and TGF-β in epithelial plasticity and potential carcinogenesis. Here, we report the role of GRHL2 in oral carcinogenesis in vivo using a novel Grhl2 knockout (KO) mouse model and the underlying mechanism involving its functional interaction with TGF-β signaling. We developed epithelial-specific Grhl2 conditional KO mice by crossing Grhl2 floxed mice with those expressing CreER driven by the K14 promoter...
May 8, 2018: Oncogenesis
Jia Xie, Hilal Gurler Main, Joelle D Sacks, Goda G Muralidhar, Maria V Barbolina
Failure of currently used cytotoxic chemotherapy is one of the main reasons behind high mortality from metastatic high grade serous ovarian carcinoma. We found that high expression of a receptor for fractalkine (CX3 CR1) significantly correlated with shorter survival of patients with serous ovarian carcinoma treated with cytotoxic DNA damage chemotherapies, and reduction of CX3 CR1 expression resulted in sensitization to several DNA damaging modalities, including x-ray radiation and cisplatin. Here, we show that CX3 CR1 plays a role in double-strand DNA break response and repair by regulating expression of RAD50 by a MYC-dependent mechanism...
May 1, 2018: Oncogenesis
Wenjing Du, Lan Ni, Baojun Liu, Ying Wei, Yubao Lv, Sujing Qiang, Jingcheng Dong, Xijun Liu
The transcriptional factor SALL4, an important stem cell regulator, is expressed in hematopoietic stem cells and various malignancies, but its role in EGFR-mutated NSCLCs has not been studied yet. Here, we report that the expression of Sal-like protein 4 (SALL4), was significantly higher in EGFR mutated lung tumors than in non-tumor tissue. SALL4-high lung cancer patients had poorer prognosis after surgery than SALL4-low patients. The expression of SALL4 could be induced by the activation of EGFR through the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway...
April 25, 2018: Oncogenesis
Anastasia Wyce, Jeanne J Matteo, Shawn W Foley, Daniel J Felitsky, Satyajit R Rajapurkar, Xi-Ping Zhang, Melissa C Musso, Susan Korenchuk, Natalie O Karpinich, Kathryn M Keenan, Melissa Stern, Lijoy K Mathew, Charles F McHugh, Michael T McCabe, Peter J Tummino, Ryan G Kruger, Christopher Carpenter, Olena Barbash
BET inhibitors exhibit broad activity in cancer models, making predictive biomarkers challenging to define. Here we investigate the biomarkers of activity of the clinical BET inhibitor GSK525762 (I-BET; I-BET762) across cancer cell lines and demonstrate that KRAS mutations are novel resistance biomarkers. This finding led us to combine BET with RAS pathway inhibition using MEK inhibitors to overcome resistance, which resulted in synergistic effects on growth and survival in RAS pathway mutant models as well as a subset of cell lines lacking RAS pathway mutations...
April 20, 2018: Oncogenesis
Amandine Bastide, Alexandre David
The ribosome has long been considered as a consistent molecular factory, with a rather passive role in the translation process. Recent findings have shifted this obsolete view, revealing a remarkably complex and multifaceted machinery whose role is to orchestrate spatiotemporal control of gene expression. Ribosome specialization discovery has raised the interesting possibility of the existence of its malignant counterpart, an 'oncogenic' ribosome, which may promote tumor progression. Here we weigh the arguments supporting the existence of an 'oncogenic' ribosome and evaluate its role in cancer evolution...
April 20, 2018: Oncogenesis
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