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Molecular Carcinogenesis

Soumaya Souid, Heba E Elsayed, Hassan Y Ebrahim, Mohamed M Mohyeldin, Abu Bakar Siddique, Habib Karoui, Khalid A El Sayed, Khadija Essafi-Benkhadir
The failure of chemotherapy especially in triple negative breast cancer (TNBC) patients has been correlated with the overexpression of the mesenchymal-epithelial transition factor (c-Met) receptor. Thus, the hepatocyte growth factor (HGF)/c-Met signaling axis has gained considerable attention as a valid molecular target for breast cancer therapy. This study reports for the first time the discovery of the 131 -oxophorbines pheophorbide A and protopheophorbide A along with chlorophyllide A from Ziziphus lotus, an edible typical Tunisian plant, as the potent antiproliferative compounds against the human breast cancer cells MDA-MB-231 and MCF-7...
July 6, 2018: Molecular Carcinogenesis
Samantha M Carlisle, Patrick J Trainor, Mark A Doll, Marcus W Stepp, Carolyn M Klinge, David W Hein
INTRODUCTION: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can also hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. Expression of NAT1 varies between individuals and is elevated in several cancers including estrogen receptor positive (ER +) breast cancers. To date however, the exact mechanism by which NAT1 expression affects mitochondrial bioenergetics in breast cancer cells has not been described...
July 2, 2018: Molecular Carcinogenesis
Farhadul Islam, Stephanie Chaousis, Riajul Wahab, Vinod Gopalan, Alfred King-Yin Lam
FAM134B is an autophagy regulator of endoplasmic reticulum and acts as a cancer suppressor in colon cancer. However, the molecular signalling pathways by which FAM134B interacts within colon carcinogenesis is still unknown. Herein, this study aims to determine the interacting partners of FAM134B for the first time in colon cancer and to explore the precise location of FAM134B in cancer signalling pathways. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) followed by anti-FAM134B co-immune precipitation of FAM134B interacting complex was used to identify the potential interactors of FAM134B in colon cancer cells...
July 2, 2018: Molecular Carcinogenesis
Chuanqing Wu, Xiaojie Zhu, Kaixiong Tao, Weizhen Liu, Tuo Ruan, Wenze Wan, Chun Zhang, Weikang Zhang
The long non-coding RNA MALAT1 has been proved to promote the cell proliferation, drug resistance, invasion and metastasis of colorectal cancer (CRC) in vitro and in vivo by regulating the expression of various oncogenes and their protein products. Our previous work discovered that the expression of the mRNA-decapping enzymes 1a (DCP1A) is upregulated in CRCs. However, the relationships between MALAT1 and DCP1A in the development of CRC and the underlying mechanisms are still unclear. In this study, we investigated the molecular mechanisms by which MALAT1 and DCP1A may be linked to contribute to the malignancies of CRCs...
July 2, 2018: Molecular Carcinogenesis
So Young Kim, MiNa Hong, Seung-Ho Heo, Sojung Park, Taeg Kyu Kwon, Young Hoon Sung, Yumin Oh, Seulki Lee, Gwan-Su Yi, Inki Kim
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been characterized as an anti-cancer therapeutic agent with prominent cancer cell selectivity over normal cells. However, breast cancer cells are generally resistant to TRAIL, thus limiting its therapeutic potential. In this study, we found that BIX-01294, a selective inhibitor of euchromatin histone methyltransferase 2/G9a, is a strong TRAIL sensitizer in breast cancer cells. The combination of BIX-01294 and TRAIL decreased cell viability and led to an increase in the annexin V/propidium iodide-positive cell population, DNA fragmentation, and caspase activation...
July 2, 2018: Molecular Carcinogenesis
Guo Dai, Shuang Deng, Weichun Guo, Ling Yu, Jian Yang, Sheng Zhou, Tian Gao
Overcoming platinum drug resistance represents a major clinical challenge in osteosarcoma (OS) treatment. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). Notch signaling is implicated in regulating CSCs and tumor resistance to platinum. Thus, we attempt to investigate whether inhibiting of Notch pathway could sensitize cisplatin (CDDP) to CDDP-resistant OS cells and the underlying molecular mechanisms. OS cell lines resistant to CDDP were treated with DAPT, CDDP or combination, we present evidences that DAPT enhances the cytotoxic effect of CDDP in resistant OS by inhibiting proliferation, resulting in G0/G1 cell-cycle arrest, inducing apoptosis, and reducing motility...
July 2, 2018: Molecular Carcinogenesis
Hack Sun Choi, Ji-Hyang Kim, Su-Lim Kim, Hong-Yuan Deng, Doseung Lee, Chang Sook Kim, Bong-Sik Yun, Dong-Sun Lee
Cancer stem cells (CSCs) as a subpopulation of cancer cells are drug-resistant and radiation-resistant cancer cells to be responsible for tumor progress, maintenance and recurrence of cancer, and metastasis. This study isolated and investigated a new cancer stem cell (CSC) inhibitor derived from lactic acid fermentation products using culture broth with 2% aronia juice. The anti-CSC activity of aronia-cultured broth was significantly higher than that of the control. Activity-guided fractionation and repeated chromatographic preparation led to the isolation of one compound...
July 2, 2018: Molecular Carcinogenesis
Mary Ellen Urick, Daphne W Bell
Serous endometrial cancers (ECs) are clinically aggressive tumors that frequently harbor somatic mutations in FBXW7 (F-box and WD repeat domain-containing 7). The FBXW7 tumor suppressor is part of a SCF (complex of SKP1, Cullin 1, F-box protein) ubiquitin ligase complex which controls the degradation of numerous substrates that, if not properly regulated, can contribute to the initiation or progression of tumorigenesis. Despite reports that up to 30% of serous ECs include somatic mutations in FBXW7, the molecular effects of mutated FBXW7 in ECs have not been determined...
July 2, 2018: Molecular Carcinogenesis
Jian Li, Amber R Smith, Rebecca T Marquez, Jun Li, Kun Li, Lan Lan, Xiaoqing Wu, Linxi Zhao, Fangli Ren, Yi Wang, Yinyin Wang, Baoqing Jia, Liang Xu, Zhijie Chang
CREPT (Cell-cycle-related and expression-elevated protein in tumor)/RPRD1B, a novel protein that enhances the transcription of Cyclin D1 to promote cell proliferation during tumorigenesis, was demonstrated highly expressed in most of tumors. However, it remains unclear how CREPT is regulated in colorectal cancers. In this study, we report that miR-383 negatively regulates CREPT expression. We observed that CREPT was up-regulated but the expression of miR-383 was down regulated in both colon cancer cell lines and colon tumor tissues...
June 25, 2018: Molecular Carcinogenesis
Hye-Rim Won, Hyun-Wook Ryu, Dong-Hee Shin, Soo-Keun Yeon, Dong Hoon Lee, So Hee Kwon
Although histone deacetylase inhibitors (HDACi) alone could be clinically useful, these are most recently used in combination with other anticancer agents in clinical trials for cancer treatment. Recently, we reported the anticancer activity of an HDAC6-selective inhibitor A452 towards various cancer cell types. This study aims to present a potent synergistic antiproliferative effect of A452/anticancer agent treatment in colorectal cancer cells (CRC) cells, independently of the p53 status. A452 in combination with irinotecan, or SAHA is more potent than either drug alone in the apoptotic pathway as evidenced by activated caspase-3 and PARP, increased Bak and pp38, decreased Bcl-xL, pERK and pAKT, and induced apoptotic cells...
June 19, 2018: Molecular Carcinogenesis
Jie Gao, Zhao Wang, Gao-Ju Wang, Na Gao, Jing Li, Yun-Fei Zhang, Jun Zhou, Hong-Xin Zhang, Qiang Wen, Han Jin, Hai-Ling Qiao
Hepatofibrosis is an important susceptibility factor for hepatocarcinogenesis. However, only a handful of cases of hepatofibrosis will develop into hepatocellular carcinoma (HCC). As cytochrome P450 2E1 (CYP2E1) is involved in the metabolism and activation of many known environmental toxicants and procarcinogens, this enzyme may play a role in the development of hepatocarcinogenesis subsequent to hepatofibrosis. Herein, we evaluated whether higher CYP2E1 activity is a risk factor for the development of hepatocarcinogenesis from hepatofibrosis...
June 19, 2018: Molecular Carcinogenesis
Guo-Jin Wu, Jun Pen, Ying Huang, Su An, Ying Liu, Yang Yang, Qian Hao, Xiao-Xi Guo, Tian-Rui Xu
Aberrant activation of the Raf-MEK-ERK pathway has frequently been associated with various cancers, especially lung cancer. However, the key regulators of this pathway are largely unknown. Using functional proteomics screening, we found that KAP1 interacts with c-Raf. Knocking out KAP1 decreased c-Raf phosphorylation at serine 259 and increased its phosphorylation at serine 338, which activated MEK and ERK. We detected higher KAP1 expression in lung cancer tissues than in normal peri-tumoral tissues. KAP1 knockdown arrested A549 lung cancer cells in the G0/G1 phase of the cell cycle and attenuated cell growth, metastasis, the epithelial-mesenchymal transition, angiogenesis, stemness, and colony formation...
June 19, 2018: Molecular Carcinogenesis
Lianmei Zhao, Ming Ma, Hao Wu, Cong Zhang, Suli Dai, Pei Dong, Bingjie Huo, Baoen Shan
p-Hydroxylcinnamaldehyde isolated from the Cochinchina momordica seed (CMSP) has been identified to inhibit growth and metastasis in oesophageal squamous cell carcinoma (ESCC) by inducing differentiation. The aim of the present study was to evaluate the effect and underlying mechanism of CMSP on 4-nitroquinoline 1-oxide (4NQO)-induced oesophageal tumourigenesis. In the present study, a mouse model of oesophageal preneoplastic lesions was established by providing 4NQO-containing drinking water to C57BL/6 mice...
June 6, 2018: Molecular Carcinogenesis
Nirmalya Sen, Allison M Cross, Philip L Lorenzi, Javed Khan, Berkley E Gryder, Suntae Kim, Natasha J Caplen
Ewing sarcoma (EWS) is a soft tissue and bone tumor that occurs primarily in adolescents and young adults. In most cases of EWS, the chimeric transcription factor, EWS-FLI1 is the primary oncogenic driver. The epigenome of EWS cells reflects EWS-FLI1 binding and activation or repression of transcription. Here, we demonstrate that EWS-FLI1 positively regulates the expression of proteins required for serine-glycine biosynthesis and uptake of the alternative nutrient source glutamine. Specifically, we show that EWS-FLI1 activates expression of PHGDH, PSAT1, PSPH, and SHMT2...
June 6, 2018: Molecular Carcinogenesis
Zhikun Liu, Qianwei Ye, Lingjiao Wu, Feng Gao, Haiyang Xie, Lin Zhou, Shusen Zheng, Xiao Xu
Metallothionein 1 (MT1s) is a family of cysteine-rich proteins with diverse functions such as metal homeostasis, oxidative stress, and carcinogenesis. However, its involvement in hepatocellular carcinoma (HCC) remains not fully understood. We aimed to explore the contribution of the individual member of MT1s to HCC. Its member mRNA levels were determined in cohort 1 of normal (n = 30), cirrhotic (n = 30), peritumoral (n = 135), and HCC (n = 135). In cohort 1, seven of 8 members were down-regulated during the transition from normal liver to HCC, and only MT1G and MT1X were correlated with tumor features and outcomes...
June 6, 2018: Molecular Carcinogenesis
Shengfeng Wang, Dezheng Huo, Temidayo O Ogundiran, Oladosu Ojengbede, Wei Zheng, Katherine L Nathanson, Barbara Nemesure, Stefan Ambs, Olufunmilayo I Olopade, Yonglan Zheng
Gene expression changes within the Hippo pathway were found to be associated with large tumor size and metastasis in breast cancer. The combined effect of genetic variants in genes of this pathway may have a causal role in breast cancer development. We examined 7086 SNPs that were not highly correlated (r2  < 0.8) in 35 Hippo pathway genes using data from the genome-wide association study of breast cancer from the Root Consortium, which includes 3686 participants of African ancestry from Nigeria, United States of America, and Barbados: 1657 cases (403 estrogen receptor-positive [ER+], 374 ER-) and 2029 controls...
June 6, 2018: Molecular Carcinogenesis
Xinzhe Li, Jintao He, Bo Li, Min Gao, Yijun Zeng, Jiqin Lian, Chunmeng Shi, Yan Huang, Fengtian He
The BH3 mimetic (-)-gossypol (-)-G has shown promising efficacy to kill several kinds of cancer cells or potentiate current chemotherapeutics. But it induces limited apoptosis in cancer cells with high level of Bcl-2. The nuclear receptor PPARγ and its agonist rosiglitazone can suppress various malignancies. More importantly, rosiglitazone is able to enhance the anti-tumor effects of chemotherapy drugs such as carboplatin and tyrosine kinase inhibitors. In this study, we for the first time demonstrated that rosiglitazone could sensitize (-)-G to induce apoptosis in cancer cells with high level of Bcl-2...
June 1, 2018: Molecular Carcinogenesis
Chenfei Huang, Zhe Cao, Jun Ma, Yi Shen, Yiwen Bu, Ramina Khoshaba, Guiyuan Shi, Dan Huang, Duan-Fang Liao, Haitao Ji, Junfei Jin, Deliang Cao
Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. However, little is known of the molecular mechanisms of action. Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. Our data showed that ectopic expression of AKR1B10 in breast cancer cells MCF-7 promoted lipogenesis and enhanced levels of lipid second messengers, including phosphatidylinositol bisphosphate (PIP2), diacylglycerol (DAG), and inositol triphosphate (IP3)...
May 30, 2018: Molecular Carcinogenesis
Zhihua Li, Zhening Pu, Jingyi Fan, Ni Li, Meng Zhu, Jiahui Zhang, Yuzhuo Wang, Liguo Geng, Yang Cheng, Hongxia Ma, Guangfu Jin, Juncheng Dai, Zhibin Hu, Hongbing Shen
Genome-wide association studies (GWAS) and fine mapping studies have identified multiple lung cancer susceptibility variants in TERT-CLPTM1L region. However, it is still unclear about the relationship between these risk variants and the independent lung cancer risk signals in this region. Therefore, we evaluated the independent susceptibility signals for lung cancer and explored the potential functional variants in this region. Sequential conditional analysis was used to detect the independent susceptibility loci based on four lung cancer GWAS datasets with 12 843 lung cases and 12 639 controls...
May 29, 2018: Molecular Carcinogenesis
Brian Z Huang, Konstantinos K Tsilidis, Michael W Smith, Judith Hoffman-Bolton, Kala Visvanathan, Elizabeth A Platz, Corinne E Joshu
We previously investigated the association between single nucleotide polymorphisms (SNPs) in genes related to obesity and inflammation and colorectal cancer in the CLUE II cohort. However, the relationships between these SNPs and colorectal adenomas have not been well evaluated. In a nested case-control study of 135 incident adenoma cases and 269 matched controls in the CLUE II cohort (1989-2000), we genotyped 17 candidate SNPs in 12 genes (PPARG, TCF7L2, ADIPOQ, LEP, IL10, CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and 19 tagSNPs in three genes (IL10, CRP, and TLR4)...
May 26, 2018: Molecular Carcinogenesis
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