Cooperative multi-targeting of signaling networks by angiomiR-204 inhibits vasculogenic mimicry in breast cancer cells
RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attractive approach in cancer. Here, we uncovered a miR-204 cooperative targeting of multiple signaling transducers involved in vasculogenic mimicry (VM). Our data showed that invasive triple negative MDA-MB-231 and Hs-578T breast cancer cells, but not poorly invasive MCF-7 cells, efficiently undergoes matrix-associated VM under hypoxia. Ectopic restoration of miR-204 in MDA-MB-231 cells leads to a potent inhibition of VM and reduction of number of branch points and patterned 3D channels. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Yarely M. Salinas-Vera, Laurence A. Marchat, Ra úl García-Vázquez, Claudia Haydée González de la Rosa, Eduardo Castañeda-Saucedo, Napoleón Navarro Tito, Carlos Palma Flores, Carlos Pérez-Plasencia, José L. Cruz-Colin, Ángeles Carlos-Reyes, José Tags: Original Articles Source Type: research
An endogenous and ectopic expression of metabotropic glutamate receptor 8 (mGluR8) inhibits proliferation and increases chemosensitivity of human neuroblastoma and glioma cells
The present study aimed to determine the role of metabotropic glutamate receptor 8 (mGluR8) in tumor biology. Using various molecular approaches (RNAi or GRM8 cDNA), cell clones with downregulated (human neuroblastoma SH-SY5Y and human glioma LN229) or overexpressed (human glioma U87-MG and LN18 cell lines) mGluR8 were generated. Next, comparative studies on cell proliferation and migration rates, induction of apoptosis and chemosensitivity were performed among these clones. The mGluR8-downregulated SH-SY5Y clones proliferated faster and were more resistant to cytotoxic action of staurosporine, doxorubicin, irinotecan and ...
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Danuta Jantas, Beata Grygier, S ławomir Gołda, Jakub Chwastek, Justyna Zatorska, Magdalena Tertil Tags: Original Articles Source Type: research
Human colorectal cancer initiation is bidirectional, and cell growth, metabolic genes and transporter genes are early drivers of tumorigenesis
The role of stem cells in the development of solid tumors remains controversial. In colorectal cancers (CRC), this is complicated by the conflicting “top-down” or “bottom-up” hypotheses of cancer initiation. We profiled the expressions of genes from the top (T) and bottom (B) crypt fractions of normal-appearing human colonic mucosa (M) at least 20 cm away from the tumor as a baseline and compared this to the genes of matched mucosa adj acent to tumors (MT) in twenty-three sporadic CRC patients. In thirteen patients, the genetic distance (M-MT) between the B fractions is smaller than the distance between the T fra...
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Yi Hong, Soo Chin Liew, Lai Fun Thean, Choong Leong Tang, Peh Yean Cheah Tags: Original Articles Source Type: research
Methylation-mediated miR-155-FAM133A axis contributes to the attenuated invasion and migration of IDH mutant gliomas
Gliomas with isocitrate dehydrogenases genes mutation (IDHMT) were found to be less aggressive than their wildtype (IDHWT) counterparts. However, the mechanism remains unclear. The current study aims to investigate the role of silenced oncogenic microRNAs in IDHMT gliomas, which were largely ignored and may contribute to the less aggressive behavior of IDHMT gliomas. Microarrays, bioinformatics analysis of the data from TCGA and qPCR analysis of samples from our experimental cohort (LGG: IDHWT=10, IDHMT=31; GBM: IDHWT=34, IDHMT=9) were performed. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Guo-Hao Huang, Lei Du, Ningning Li, Ying Zhang, Yan Xiang, Jun-Hai Tang, Shuli Xia, Eric Erquan Zhang, Sheng-Qing Lv Tags: Original Articles Source Type: research
IGFBP2 promotes salivary adenoid cystic carcinoma metastasis by activating the NF- κB/ZEB1 signaling pathway
In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF- κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Xiaofeng Yao, Yu Wang, Yuansheng Duan, Qiang Zhang, Ping Li, Rui Jin, Yingjie Tao, Wenchao Zhang, Xudong Wang, Chao Jing, Xuan Zhou Tags: Original Articles Source Type: research
Antitumor activity of nanoliposomes encapsulating the novobiocin analog 6BrCaQ in a triple-negative breast cancer model in mice
In this study, we investigated the anticancer efficacy of pegylated liposomes containing 6BrCaQ, an hsp90 inhibitor derived from novobiocin. 6BrCaQ has been previously identified as the most potent compound in a series of quinoleic novobiocin analogs but is poorly water-soluble. We investigated, for the first time, the anti-proliferative effects of this drug in vivo in an orthotopic breast cancer model (MDA-MB-231 luc) using pegylated liposomes to allow its administration. Hsp90, hsp70 and hsp27 protein and mRNA expressions were not strongly affected after treatment meaning it did not induce a heat shock response often ass...
Source: Cancer Letters - June 5, 2018 Category: Cancer & Oncology Authors: F élix Sauvage, Elias Fattal, Walhan Al-Shaer, Stéphanie Denis, Emilie Brotin, Christophe Denoyelle, Cécile Blanc-Fournier, Balthazar Toussaint, Samir Messaoudi, Mouad Alami, Gillian Barratt, Juliette Vergnaud-Gauduchon Tags: Original Articles Source Type: research
Antitumor activity of nanoliposomes encapsulating the novobiocin analogue 6BrCaQ in a triple-negative breast cancer model in mice
In this study, we investigated the anticancer efficacy of pegylated liposomes containing 6BrCaQ, an hsp90 inhibitor derived from novobiocin. 6BrCaQ has been previously identified as the most potent compound in a series of quinoleic novobiocin analogs but is poorly water-soluble. We investigated, for the first time, the anti-proliferative effects of this drug in vivo in an orthotopic breast cancer model (MDA-MB-231 luc) using pegylated liposomes to allow its administration. Hsp90, hsp70 and hsp27 protein and mRNA expressions were not strongly affected after treatment meaning it did not induce a heat shock response often ass...
Source: Cancer Letters - June 5, 2018 Category: Cancer & Oncology Authors: F élix Sauvage, Elias Fattal, Walhan Al-Shaer, Stéphanie Denis, Emilie Brotin, Christophe Denoyelle, Cécile Blanc-Fournier, Balthazar Toussaint, Samir Messaoudi, Mouad Alami, Gillian Barratt, Juliette Vergnaud-Gauduchon Tags: Original Articles Source Type: research
Precision medicine approaches may be the future for CRLF2 rearranged Down Syndrome Acute Lymphoblastic Leukaemia patients
Breakthrough studies over the past decade have uncovered unique gene fusions implicated in acute lymphoblastic leukaemia (ALL). The critical gene, cytokine receptor-like factor 2 (CRLF2), is rearranged in 5 –16% of B-ALL, comprising 50% of Philadelphia-like ALL and cooperates with genomic lesions in the Jak, Mapk and Ras signalling pathways. Children with Down Syndrome (DS) have a predisposition to developing CRLF2 rearranged-ALL which is observed in 60% of DS-ALL patients. These patients experience a poor survival outcome. (Source: Cancer Letters)
Source: Cancer Letters - June 4, 2018 Category: Cancer & Oncology Authors: Elyse C. Page, Susan L. Heatley, David T. Yeung, Paul Q. Thomas, Deborah L. White Tags: Mini-review Source Type: research
Anti-angiogenesis effect of Neferine via regulating autophagy and polarization of tumor-associated macrophages in high-grade serous ovarian carcinoma
In this study, we found Neferine could inhibit the angiogenesis of ovarian cancer cells both in vitro and in vivo. Further analysis revealed that its suppressive effect on human umbilical vein endothelial cell (HUVEC) proliferation correlated with promoting cell cycle arrest and autophagy. The cell cycle genes were dose-dependently reduced and the level of LC3II/LC3I (microtubule associated protein 1 light chain 3) was increased. (Source: Cancer Letters)
Source: Cancer Letters - June 4, 2018 Category: Cancer & Oncology Authors: Qing Zhang, Yinuo Li, Chunying Miao, Yuqiong Wang, Ying Xu, Ruifen Dong, Zhiwei Zhang, Brannan B. Griffin, Xingsheng Yang, Zhaojian Liu, Beihua Kong Tags: Original Articles Source Type: research
A CRISPR-Cas13a system for efficient and specific therapeutic targeting of mutant KRAS for pancreatic cancer treatment
Mutant KRAS is a known driver oncogene in pancreatic cancer. However, this protein remains an “undruggable” therapeutic target. Inhibiting mutated KRAS expression at the mRNA level is a potentially effective strategy. Recently, a novel CRISPR-Cas effector, Cas13a has been reported to specifically knock down mRNA expression under the guidance of a single CRISPR-RNA in mammalian cells. Her e we demonstrate that the CRISPR-Cas13a system can be engineered for targeted therapy of mutant KRAS in pancreatic cancer. (Source: Cancer Letters)
Source: Cancer Letters - June 2, 2018 Category: Cancer & Oncology Authors: Xiao Zhao, Liang Liu, Jiayan Lang, Keman Cheng, Yongwei Wang, Xueyan Li, Jian Shi, Yanli Wang, Guangjun Nie Tags: Original Articles Source Type: research
RASSF6-mediated inhibition of Mcl-1 through JNK activation improves the anti-tumor effects of sorafenib in renal cell carcinoma
Ras association domain family member 6 (RASSF6) has been shown to act as a tumor suppressor and predictor of poor prognosis in renal cell carcinoma (RCC). However, little is known about the effects of RASSF6 on sorafenib resistance or the underlying mechanism. Here, we show that RASSF6 expression positively correlates with sorafenib sensitivity in RCC cells and human samples. Stable ectopic overexpression of RASSF6 in RCC cell lines reduces resistance to sorafenib in vitro and in vivo. At a molecular level, RASSF6 activates the JNK signaling pathway, which further contributes to Mcl-1 inhibition. (Source: Cancer Letters)
Source: Cancer Letters - June 1, 2018 Category: Cancer & Oncology Authors: Ying-Ying Liang, Xu-Bin Deng, Li-Si Zeng, Xian-Tao Lin, Xun-Fan Shao, Bin Wang, Zhi-Wen Mo, Ya-Wei Yuan Tags: Original Articles Source Type: research
Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - May 31, 2018 Category: Cancer & Oncology Source Type: research
Pyrazolo[1,5-a]pyrimidine TRPC6 Antagonists for the Treatment of Gastric Cancer
Transient receptor potential canonical 6 (TRPC6) proteins form receptor-operated Ca2+-permeable channels, which have been thought to bring benefit to the treatment of diseases, including cancer. However, selective antagonists for TRPC channels are rare and none of them has been tested against gastric cancer. Compound 14a and analogs were synthesized by chemical elaboration of previously reported TRPC3/6/7 agonist 4o. 14a had very weak agonist activity at TRPC6 expressed in HEK293 cells but exhibited strong inhibition on both 4o-mediated and receptor-operated activation of TRPC6 with an IC50 of about 1 μM. (Source: Cancer Letters)
Source: Cancer Letters - May 31, 2018 Category: Cancer & Oncology Authors: Mingmin Ding, Hongbo Wang, Chunrong Qu, Fuchun Xu, Yingmin Zhu, Guangyao Lv, Yungang Lu, Qingjun Zhou, Hui Zhou, Xiaodong Zeng, Jingwen Zhang, Chunhong Yan, Jiacheng Lin, Huai-Rong Luo, Zixing Deng, Yuling Xiao, Jinbin Tian, Michael X. Zhu, Xuechuan Hong Tags: Original Articles Source Type: research
MicroRNA-mediated immune regulation in rheumatic diseases
MicroRNAs (miRNAs) are endogenous small, non-coding RNAs that regulate genome expression at the post-transcriptional level. They are involved in a wide range of physiological processes including the maintenance of immune homeostasis and normal function. Accumulating evidence from animal studies show that alterations in pan or specific miRNA expression would break immunological tolerance, leading to autoimmunity. Differential miRNA expressions have also been documented in patients of many autoimmune disorders. (Source: Cancer Letters)
Source: Cancer Letters - May 31, 2018 Category: Cancer & Oncology Authors: Ian Kar Yin Lam, Jia Xin Chow, Chak Sing Lau, Vera Sau Fong Chan Tags: Mini-review Source Type: research
The hypoxic tumor microenvironment in vivo selects tumor cells with increased survival against genotoxic stresses
Tumor sensitivity to radiation therapy has been known to be dependent on O2 concentrations. However, radiosensitivity of naturally occurring hypoxic tumor cells remains to be well fully investigated in direct comparison to that of their adjacent non-hypoxic tumor cells within the same tumor. We developed a hypoxia-sensing xenograft model using the hypoxia-response element (HRE)-driven enhanced green fluorescence protein (EGFP) as a hypoxia reporter to identify hypoxic tumor cells in situ. Here, we have found that naturally hypoxic tumor cells are moderately radioresistant compared to their neighboring non-hypoxic tumor cel...
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Hoon Kim, Qun Lin, Zhong Yun Tags: Original Articles Source Type: research
