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Cancer Letters

Zhipeng Xu, Zheng Li, Weizhi Wang, Yiwen Xia, Zhongyuan He, BoWen Li, Sen Wang, Xiaoxu Huang, Guangli Sun, Jianghao Xu, Lu Wang, Qiang Zhang, Qiang Li, Jialun Lv, Linjun Wang, Lu Zhang, Diancai Zhang, Hao Xu, Zekuan Xu
Increasing evidence indicates that microRNAs (miRNAs) play an important role in various tumors by regulating downstream target genes and diverse signaling pathways. Herein, we confirmed miR-1265 expression in gastric cancer (GC) using the Cancer Genome Atlas (TCGA) database and assessed the level of miR-1265 expression in clinical specimens and cell lines. We found that miR-1265 expression was negatively correlated with tumor size. Further functional analysis revealed that miR-1265 suppresses cellular proliferation and autophagy while inducing apoptosis in GC cells...
February 16, 2019: Cancer Letters
Christos Masaoutis, Penelope Korkolopoulou, Stamatios Theocharis
Exosomes are cell-secreted extracellular vesicles, which contain an array of biomolecules, such as proteins, mRNAs, microRNAs, and lipids, take part in intercellular communication and mediate tumor-host interactions. They are increasingly considered as a source of biomarkers for liquid biopsies as well as potential drug vectors. Sarcomas are rare malignant mesenchymal tumours and due to their relative rarity exosomes have not been investigated in as extensively as in epithelial malignancies. Nonetheless, valuable information has been gathered over the last years on the roles of exosomes in sarcomas...
February 16, 2019: Cancer Letters
Fang Wei, Tong Zhang, Shu-Chou Deng, Jian-Chang Wei, Ping Yang, Qiang Wang, Zhuan-Peng Chen, Wang-Lin Li, Hua-Cui Chen, He Hu, Jie Cao
PD-L1 is critical for tumor cell escape from immune surveillance by inhibiting T cell function via the PD-1 receptor. Accumulating evidence demonstrates that anti-PD-L1 monoclonal antibodies might potently enhance antitumor effects in various tumors, but the effect of PD-L1 on colorectal cancer stem cells (CSCs) remains unclear. We observed high PD-L1 expression in CD133+ CD44+ colorectal CSCs and CSC-enriched tumorspheres. Altering PD-L1 expression promoted colorectal CSC self-renewal by increasing the expression of stemness genes, the CD133+ CD44+ cell population sizes and the ability to form tumorspheres...
February 15, 2019: Cancer Letters
Yosuke Kawahara, Takuya Furuta, Hemragul Sabit, Sho Tamai, Dong Yu, Shabierjiang Jiapaer, Jiakang Zhang, Guangtao Zhang, Masahiro Oishi, Katsuyoshi Miyashita, Yasuhiko Hayashi, Mitsutoshi Nakada
Of the erythropoietin-producing human hepatocellular receptors (Ephs), EphB4 has recently emerged as a potential target in several cancers due to its roles in modified cell migration and invasion. As little is known about the roles of EphB4 in glioma, we sought to investigate its function in glioma by in vitro cell migration and invasion assays, immunoblotting and immunostaining. EphB4 was expressed in glioma cell lines and stem-like cell lines. The stimulation of glioma cells with ephrin-B2, the sole ligand of EphB4, conducted EphB4 phosphorylation and suppressed migration and invasion that downregulation of EphB4 using small interfering RNA abrogated...
February 15, 2019: Cancer Letters
Yu Wang, Kai Wang, Yang Jin, Xia Sheng
The endoplasmic reticulum (ER) is the primary organelle responsible for the synthesis, modification, folding and secretion of proteins, especially in specialized secretory cells. It also contributes to the maintenance of cellular functions, such as Ca2+ storage, lipogenesis, gluconeogenesis, and organelle biogenesis. Cellular stress conditions, such as glucose deprivation, hypoxia and disturbance of Ca2+ homeostasis, may increase the risk of protein misfolding and perturb proteostasis. This activates ER stress and triggers the unfolded protein response (UPR), leading to either the restoration of homeostasis or cell death...
February 15, 2019: Cancer Letters
Portia A Vliet-Gregg, Kristin L Robinson, Justine Levan, Lisa R Matsumoto, Rachel A Katzenellenbogen
A significant contributor to women's cancer mortality worldwide is cervical cancer, which is caused by high-risk human papillomavirus (HR HPV). The two viral oncoproteins of HR HPV, E6 and E7, partner with host cell proteins to target oncogenic proteins and pathways. Previously, we have shown HR HPV type 16 E6 (16E6) interacts with the host protein NFX1-123 to target telomerase and cellular immortalization, requiring NFX1-123 to fully upregulate telomerase activity. We now report that NFX1-123 is highly expressed in primary cervical cancers...
February 15, 2019: Cancer Letters
Jay H Fowke, Tatsuki Koyama, Qi Dai, S Lilly Zheng, Jianfeng Xu, Lauren E Howard, Stephen J Freedland
Recent studies suggest a diet low in dietary magnesium intake or lower blood magnesium levels is linked with increased prostate cancer risk. This study investigates the race-specific link between blood magnesium and calcium levels, or dietary magnesium intake, and the diagnosis of low-grade and high-grade prostate cancer. The study included 637 prostate cancer cases and 715 biopsy-negative controls (50% black) recruited from Nashville, TN or Durham, NC. Blood was collected at the time of recruitment, and dietary intake was assessed by food frequency questionnaire...
February 15, 2019: Cancer Letters
Bo Jiang, Wei Chen, Haixiang Qin, Wenli Diao, Binghua Li, Wenmin Cao, Zhenxing Zhang, Wei Qi, Jie Gao, Mengxia Chen, Xiaozhi Zhao, Hongqian Guo
Studies on the mechanism of clear cell renal cell carcinoma (ccRCC) progression are lacking. In this study, TOX3 was identified as a novel cancer suppressor gene in ccRCC. Hypermethylation of CpG probes in the promoter region was associated with the functional loss of TOX3 in ccRCC cancer tissues. Downregulation of TOX3 mRNA was strongly associated with poor clinical outcomes in ccRCC. Immunohistochemistry confirmed TOX3 was downregulated in primary tumors without metastasis (n=126) and further downregulated in primary metastatic tumors (n=23) compared with adjacent noncancerous tissues (n=92)...
February 14, 2019: Cancer Letters
Qin Wang, Lei Dai, Yuan Wang, Jie Deng, Yi Lin, Qingnan Wang, Chao Fang, Zida Ma, Huiling Wang, Gang Shi, Lin Cheng, Yi Liu, Shuang Chen, Junshu Li, Zhexu Dong, Xiaolan Su, Lie Yang, Shuang Zhang, Ming Jiang, Meijuan Huang, Yang Yang, Dechao Yu, Zongguang Zhou, Yuquan Wei, Hongxin Deng
SARI (suppressor of activator protein 1, regulated by IFN) functions as a tumour suppressor and is inactivated in various cancers. However, the mechanism underlying SARI inactivation in cancer remains elusive. In this study, we detected a high level of DNA methylation of the SARI promoter and an inverse correlation between SARI promoter methylation and expression in malignant tissues from patients with colon cancer. Furthermore, we found that the SARI promoter methylation status is a prognostic indicator for patients with colon cancer...
February 13, 2019: Cancer Letters
Po-Hsuan Su, Yaw-Wen Hsu, Rui-Lan Huang, Lin-Yu Chen, Tai-Kuang Chao, Chi-Chun Liao, Chien-Wen Chen, Tzu-I Wu, Shih-Peng Mao, Curt Balch, Hung-Cheng Lai
DNA hypermethylation is a driving force in carcinogenesis. However, the role of active DNA hypomethylation in cancer remains largely unknown. This process, facilitated by ten-eleven translocation methylcytosine dioxygenase 1 (TET1), which oxidizes 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), has never been studied in cervical cancer. Here, we found that TET1 and 5hmC correlative increases from normal cervix to Low-grade squamous intraepithelial lesion (LSIL), maximizing in High-grade squamous intraepithelial lesion (HSIL), and decreasing in invasive cancer...
February 13, 2019: Cancer Letters
Yuqing Yang, Renyi Wu, Davit Sargsyan, Ran Yin, Hsiao-Chen Kuo, Irene Yang, Lujing Wang, David Cheng, Chao Wang, Shanyi Li, Rasika Hudlikar, Yaoping Lu, Ah-Ng Kong
Exposure to ultraviolet B (UVB) irradiation results in multitude of cellular responses including generation of reactive oxygen species and DNA damage and is responsible for non-melanoma skin cancers (NMSCs). Although genetic mutation is well documented, the epi-mutation, the alteration in epigenetics, remains elusive. In this study, we utilized CpG Methyl-seq to identify a genome-wide DNA CpG methylation, to profile the DNA methylation in UVB-irradiated SKH-1 mouse skin epidermis and non-melanoma skin papillomas at various stages...
February 13, 2019: Cancer Letters
Lu Wang, Kai Li, Xianjie Lin, Zhimeng Yao, Shuhong Wang, Xiao Xiong, Zhifeng Ning, Jing Wang, Xiaozheng Xu, Yi Jiang, Ditian Liu, Yuping Chen, Dianzheng Zhang, Hao Zhang
Evasion of apoptosis is a major contributing factor to the development of chemo- and radiotherapy resistance. Therefore, activation of non-apoptotic programmed cell death (PCD) could be an effective alternative against apoptosis-resistant cancers. In this study, we demonstrated in vitro and in vivo that metformin can induce pyroptosis, a non-apoptotic PCD, in esophageal squamous cell carcinoma (ESCC), a commonly known chemo-refractory cancer, especially at its advanced stages. Proline-, glutamic acid- and leucine-rich protein-1 (PELP1) is a scaffolding oncogene and upregulated PELP1 in advanced stages of ESCC is highly associated with cancer progression and patient outcomes...
February 13, 2019: Cancer Letters
Yuan Zhang, Wei Zhao, Sheng Li, Mengzhu Lv, Xiaodan Yang, Meng Li, Zhiqian Zhang
Tumor-initiating cells (TICs), which are responsible for sustaining tumor growth and recurrence, rely on several regulatory factors. However, the mechanism of inflammation-related molecules in the acquisition and maintenance of TIC properties in hepatocellular carcinoma (HCC) remains elusive. We previously demonstrated that the voltage-gated calcium channel α2δ1 subunit is a functional surface marker of HCC TICs. Here, we found that the expression of an inflammation-related molecule C-X-C motif chemokine 11 (CXCL11) was significantly upregulated in α2δ1+ HCC TICs and that CXCL11 induced the expression of stem cell-related genes, such as BMI1, NANOG, MDR1, ABCG2, and CACNA2D1...
February 13, 2019: Cancer Letters
Lévêque Romain, Corbet Cyril, Aubert Léo, Guilbert Matthieu, Lagadec Chann, Adriaenssens Eric, Duval Jérémy, Finetti Pascal, Birnbaum Daniel, Magné Nicolas, Chopin Valérie, Bertucci François, Le Bourhis Xuefen, Toillon Robert-Alain
ProNGF expression has been linked to several types of cancers including breast cancer, and we have previously shown that proNGF stimulates breast cancer invasion in an autocrine manner through membrane receptors sortilin and TrkA. However, little is known regarding TrkA-associated protein partners upon proNGF stimulation. By proteomic analysis and proximity ligation assays, we found that proNGF binding to sortilin induced sequential formation of the functional sortilin/TrkA/EphA2 complex, leading to TrkA-phosphorylation dependent Akt activation and EphA2-dependent Src activation...
February 13, 2019: Cancer Letters
Kamal Ahmed, Alexey Koval, Jiabin Xu, Alexandre Bodmer, Vladimir L Katanaev
Wnt signaling is overactivated in triple-negative breast cancer (TNBC) and several other cancers, and its suppression emerges as an effective anticancer treatment. However, no drugs targeting the Wnt pathway exist on the market nor in advanced clinical trials. Here we provide a comprehensive body of preclinical evidence that an anti-leprotic drug clofazimine is effective against TNBC. Clofazimine specifically inhibits canonical Wnt signaling in a panel of TNBC cells in vitro. In several mouse xenograft models of TNBC, clofazimine efficiently suppresses tumor growth, correlating with in vivo inhibition of the Wnt pathway in the tumors...
February 13, 2019: Cancer Letters
Yongmei Feng, E Hampton Sessions, Fan Zhang, Fuqiang Ban, Veronica Placencio-Hickok, Chen-Ting Ma, Fu-Yue Zeng, Ian Pass, David B Terry, Gregory Cadwell, Laurie A Bankston, Robert C Liddington, Thomas D Y Chung, Anthony B Pinkerton, Eduard Sergienko, Martin Gleave, Neil Bhowmick, Michael R Jackson, Artem Cherkasov, Ze'ev A Ronai
Inhibition of ubiquitin ligases with small molecule remains a very challenging task, given the lack of catalytic activity of the target and the requirement of disruption of its interactions with other proteins. Siah1/2, which are E3 ubiquitin ligases, are implicated in melanoma and prostate cancer and represent high-value drug targets. We utilized three independent screening approaches in our efforts to identify small-molecule Siah1/2 inhibitors: Affinity Selection-Mass Spectrometry, a protein thermal shift-based assay and an in silico based screen...
February 13, 2019: Cancer Letters
Diana C Márquez-Garbán, Manuel Gorrín-Rivas, Hsiao-Wang Chen, Colin Sterling, David Elashoff, Nalo Hamilton, Richard J Pietras
Angiogenesis is critical for breast cancer progression. Overexpression of HER-2/neu receptors occur in 25-30% of breast cancers, and treatment with trastuzumab inhibits HER-2-overexpressing tumor growth. Notably, HER-2-mediated signaling enhances vascular endothelial growth factor (VEGF) secretion to increase tumor-associated angiogenesis. Squalamine (aminosterol compound) suppresses VEGF-induced activation of kinases in vascular endothelial cells and inhibits tumor-associated angiogenesis. We assessed antitumor effects of squalamine either alone or with trastuzumab in nude mice bearing breast tumor xenografts without (MCF-7) or with HER2-overexpression (MCF-7/HER-2)...
February 13, 2019: Cancer Letters
Farrukh Aqil, Radha Munagala, Jeyaprakash Jeyabalan, Ashish K Agrawal, Al-Hassan Kyakulaga, Sarah A Wilcher, Ramesh C Gupta
Gene-silencing with targeted siRNAs has great potential as a therapeutic approach for various diseases including cancer. However, intracellular delivery of siRNA is challenging. We used bovine milk exosomes as a novel system for siRNA delivery. First, we demonstrated that exosomes can deliver endogenous RNA payloads into recipient cells. Next, we loaded siRNA against specific genes including VEGF, EGFR, AKT, MAPK, and KRAS. We utilized 5'-32 P-labeled siKRAS as a tracer and found exosome loading with siRNA could be variable...
February 13, 2019: Cancer Letters
Yexiong Li, Qinfu Feng, Jing Jin, Susheng Shi, Zhihui Zhang, Xu Che, Jianwei Zhang, Yingtai Chen, Xiuhong Wu, Rufu Chen, Shengping Li, Jing Wang, Guang Li, Fei Li, Menghua Dai, Lei Zheng, Chengfeng Wang
Pancreatic cancer (PC), one of the most lethal malignancies, accounts for 8% to 10% of digestive system cancers, and the incidence is increasing. Surgery, chemotherapy, and radiotherapy have been the main treatment methods but are not very effective. However, only 20% of patients have the opportunity to undergo surgical operation. Approximately 30-40% of patients present with locally advanced, unresectable pancreatic cancer because of invasion of mesenteric vessels or adjacent organs. The first patient with unresectable pancreatic cancer was treated with Intraoperative radiotherapy (IORT) in 1959[ 1 ] ...
February 13, 2019: Cancer Letters
Jinhuan Wu, Yuping Chen, Guohe Geng, Lei Li, Ping Yin, Somaira Nowsheen, Yunhui Li, Chenming Wu, Jiaqi Liu, Fei Zhao, Wootae Kim, Qin Zhou, Jinzhou Huang, Guijie Guo, Chao Zhang, Xinyi Tu, Xiumei Gao, Zhenkun Lou, Kuntian Luo, Haixuan Qiao, Jian Yuan
The serine/threonine kinase, CHK2 (checkpoint kinase 2), is a key mediator in DNA damage response and a tumor suppressor, which is implicated in promoting cell cycle arrest, apoptosis and DNA repair. Accumulating evidence suggests that these functions are primarily exerted through phosphorylation downstream factors such as p53 and BRCA1. Recent studies have shown that ubiquitination is an important mode of regulation of CHK2. However, it remains largely unclear whether deubiquitinases participate in regulation of CHK2...
February 13, 2019: Cancer Letters
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