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https://www.readbyqxmd.com/read/28087810/akt1-lkb1-and-yap1-revealed-as-myc-interactors-with-nanoluc-based-protein-fragment-complementation-assay
#1
Xiu-Lei Mo, Qi Qi, Andrei A Ivanov, Qiankun Niu, Yin Luo, Jonathan Havel, Russell Goetze, Sydney Bell, Carlos S Moreno, Lee A D Cooper, Margaret A Johns, Fadlo R Khuri, Yuhong Du, Haian Fu
The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. Here we report the development of a NanoLuc®-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#2
Zhimin Gu, Jiliang Xia, Hongwei Xu, Ivana Frech, Guido Tricot, Fenghuang Zhan
BACKGROUND: Aerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival. METHODS: Tandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28081224/resveratrol-impairs-glioma-stem-cells-proliferation-and-motility-by-modulating-the-wnt-signaling-pathway
#3
Chiara Cilibrasi, Gabriele Riva, Gabriele Romano, Massimiliano Cadamuro, Riccardo Bazzoni, Valentina Butta, Laura Paoletta, Leda Dalprà, Mario Strazzabosco, Marialuisa Lavitrano, Roberto Giovannoni, Angela Bentivegna
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits...
2017: PloS One
https://www.readbyqxmd.com/read/28078190/loss-of-quiescence-and-self-renewal-capacity-of-hematopoietic-stem-cell-in-an-in-vitro-leukemic-niche
#4
Natalia-Del Pilar Vanegas, Jean-Paul Vernot
BACKGROUND: Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. METHODS: A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28077837/curcumin-inhibits-gastric-carcinoma-cell-growth-and-induces-apoptosis-by-suppressing-the-wnt-%C3%AE-catenin-signaling-pathway
#5
Ruzhen Zheng, Qinghua Deng, Yuehua Liu, Pengjun Zhao
BACKGROUND Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/b-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. MATERIAL AND METHODS We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay...
January 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28076844/sulforaphane-inhibits-cancer-stem-like-cell-properties-and-cisplatin-resistance-through-mir-214-mediated-downregulation-of-c-myc-in-non-small-cell-lung-cancer
#6
Qian-Qian Li, You-Ke Xie, Yue Wu, Lin-Lin Li, Ying Liu, Xiao-Bo Miao, Qiu-Zhen Liu, Kai-Tai Yao, Guang-Hui Xiao
We herein report that sulforaphane (SFN), a potent anti-cancer and well-tolerated dietary compound, inhibits cancer stem-like cell (CSC) properties and enhances therapeutic efficacy of cisplatin in human non-small cell lung cancer (NSCLC). SFN exerted these functions through upregulation of miR-214, which in turn targets the coding region of c-MYC. This finding was further corroborated by our observations that plasmid or lentiviral vector-mediated expression of 3'UTR-less c-MYC cDNA and cisplatin- or doxorubicin-induced endogenous c-MYC accumulation was similarly suppressed by either SFN or miR-214...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076379/upregulation-of-far-upstream-element-binding-protein-1-fubp1-promotes-tumor-proliferation-and-tumorigenesis-of-clear-cell-renal-cell-carcinoma
#7
Junyao Duan, Xu Bao, Xin Ma, Yu Zhang, Dong Ni, Hanfeng Wang, Fan Zhang, Qingshan Du, Yang Fan, Jianwen Chen, Shengpan Wu, Xintao Li, Yu Gao, Xu Zhang
OBJECTIVE: The far upstream element (FUSE)-binding protein 1 (FUBP1) is a transactivator of human c-myc proto-oncogene transcription, with important roles in carcinogenesis. However, the expression pattern and potential biological function of FUBP1 in clear cell renal cell carcinoma (ccRCC) is yet to be established. METHODS: FUBP1 expression was detected in ccRCC tissues and cell lines by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The correlations of FUBP1 mRNA expression levels with clinicopathological factors were evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28075459/death-associated-protein-kinase-3-controls-the-tumor-progression-of-a549-cells-through-erk-mapk-c-myc-signaling
#8
Satoru Kake, Tatsuya Usui, Takashi Ohama, Hideyuki Yamawaki, Koichi Sato
Death-associated protein kinases (DAPKs) are members of the serine/threonine protein kinase family, which regulate cell death. Although DAPK3 has been implicated as a tumor suppressor, a recent study revealed an oncogenic role of DAPK3. However, the role of DAPK3 in non-small cell lung cancer (NSCLC) remains unclear. Therefore, we examined whether DAPK3 controls the progression of NSCLC using the NSCLC cell line, A549. We generated A549 cells stably expressing small hairpin RNA (shRNA) targeting DAPK3. In the A549 cells, the protein level of DAPK3 was decreased and the cell proliferation was inhibited...
January 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074910/myosin-phosphatase-and-rhoa-activated-kinase-modulate-arginine-methylation-by-the-regulation-of-protein-arginine-methyltransferase-5-in-hepatocellular-carcinoma-cells
#9
Adrienn Sipos, Judit Iván, Bálint Bécsi, Zsuzsanna Darula, István Tamás, Dániel Horváth, Katalin F Medzihradszky, Ferenc Erdődi, Beáta Lontay
Myosin phosphatase (MP) holoenzyme is a protein phosphatase-1 (PP1) type Ser/Thr specific enzyme that consists of a PP1 catalytic (PP1c) and a myosin phosphatase target subunit-1 (MYPT1). MYPT1 is an ubiquitously expressed isoform and it targets PP1c to its substrates. We identified the protein arginine methyltransferase 5 (PRMT5) enzyme of the methylosome complex as a MYPT1-binding protein uncovering the nuclear MYPT1-interactome of hepatocellular carcinoma cells. It is shown that PRMT5 is regulated by phosphorylation at Thr80 by RhoA-associated protein kinase and MP...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073841/activation-of-eif4e-by-aurora-kinase-a-depicts-a-novel-druggable-axis-in-everolimus-resistant-cancer-cells
#10
Ahmed Katsha, Lihong Wang, Janet Arras, Omar M Omar, Jeffrey A Ecsedy, Abbes Belkhiri, Wael El-Rifai
PURPOSE: In this study, we investigated the role of Aurora kinase A (AURKA) in regulating EIF4E, cap-dependent translation, and resistance to mTOR inhibitor, RAD001 (everolimus). EXPERIMENTAL DESIGN: Tumor xenografts and in vitro cell models of upper gastrointestinal adenocarcinomas (UGCs) were used to determine the role of AURKA in activation of EIF4E and cap-dependent translation. Overexpression, knockdown, and pharmacologic inhibition of AURKA were used in vitro and in vivo...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28069813/residues-in-the-recq-c-terminal-domain-of-the-human-werner-syndrome-helicase-are-involved-in-unwinding-g-quadruplex-dna
#11
Amit Ketkar, Markus Voehler, Tresor Mukiza, Robert L Eoff
The structural and biophysical properties typically associated with G-quadruplex (G4) structures renders them a significant block for DNA replication, which must be overcome for cell division to occur. The Werner syndrome protein (WRN) is a RecQ-family helicase that has been implicated in the efficient processing of G4 DNA structures. The aim of the current study was to identify the residues of WRN involved in the binding and ATPase-driven unwinding of G4 DNA. Using a c-Myc G4 DNA model sequence and recombinant WRN, we have determined that the RecQ-C-terminal (RQC) domain of WRN imparts a 2-fold preference for binding to G4 DNA relative to non-G4 DNA substrates...
January 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069548/long-noncoding-rna-hulc-promotes-cell-proliferation-by-regulating-pi3k-akt-signaling-pathway-in-chronic-myeloid-leukemia
#12
Yinghao Lu, Yan Li, Xiao Chai, Qian Kang, Peng Zhao, Jie Xiong, Jishi Wang
Aberrant expression of long noncoding RNA (lncRNA) HULC is associated with various human cancers. However, the role of HULC in chronic myeloid leukemia (CML) is unknown. In this study, we found that HULC was remarkably overexpressed in both leukemia cell lines and primary hematopoietic cells derived from CML patients. The increase in HULC expression was positively correlated with clinical stages in CML. Moreover, the knockdown of HULC significantly inhibited CML cell proliferation and induced apoptosis by repressing c-Myc and Bcl-2...
January 6, 2017: Gene
https://www.readbyqxmd.com/read/28068638/knockdown-of-foxr2-suppresses-the-tumorigenesis-growth-and-metastasis-of-prostate-cancer
#13
Weibo Xu, Junkai Chang, Guangchao Liu, Xinyi Du, Xiaodong Li
Fork-head box R2 (FOXR2), a member of FOX protein family, was reported to play important roles in the development and progression of cancers. However, the expression and function of FOXR2 in prostate cancer remain unclear. In this study, we investigated the role of FOXR2 in prostate cancer and cancer progression including the molecular mechanism that drives FOXR2-mediated oncogenesis. Our results showed that FOXR2 was overexpressed in prostate cancer cell lines. The in vitro experiments demonstrated that knockdown of FOXR2 significantly repressed the proliferation, migration and invasiveness of prostate cancer cells...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28062358/alterations-in-transcription-and-protein-expressions-of-hcc-related-genes-in-hepg2-cells-caused-by-microcystin-lr
#14
Xiaoyu Li, Xiangyang Zhang, Wenjie Xie, Chune Zhou, Yao Li, Xiuhua Zhang
Microcystin-LR (MC-LR) is the most common and toxic hepatotoxin and it could induce human hepatitis and hepatocellular carcinoma (HCC) via the route of drinking water. The aim of the present study was to determine the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras and tumor suppressor gene PTEN in HepG2 cells following MC-LR-exposure to understand the possible mechanism of MC-LR-related human primary liver cancer. The results of qPCR and Western blotting showed that MC-LR-exposure at non- or sub-cytotoxic concentrations promoted the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras while suppressed tumor-suppressor gene PTEN in HepG2 cells at both transcription and protein levels...
January 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28061447/the-combination-effect-of-homoharringtonine-and-ibrutinib-on-flt3-itd-mutant-acute-myeloid-leukemia
#15
Xia Li, Xiufeng Yin, Huafeng Wang, Jiansong Huang, Mengxia Yu, Zhixin Ma, Chenying Li, Yile Zhou, Xiao Yan, ShuJuan Huang, Jie Jin
Acute myeloid leukemia (AML) is a highly heterogeneous disease and internal tandem duplication mutation in FMS-like tyrosine-kinase-3 (FLT3-ITD) has a negative impact on outcome. Finding effective treatment regimens is desperately needed. In this study, we explored the inhibitory effect and mechanism of homoharringtonine (HHT) in combination with ibrutinib on FLT3-ITD mutant AML cells. Consequently, we observed a synergistic inhibitory effect when ibrutinib was combined with HHT to inhibit cell proliferation, induce apoptosis and arrest cell cycle at G0/G1 phase in MV4-11 and MOLM-13 leukemia cells...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060381/kctd2-an-adaptor-of-cullin3-e3-ubiquitin-ligase-suppresses-gliomagenesis-by-destabilizing-c-myc
#16
Eun-Jung Kim, Sung-Hak Kim, Xiong Jin, Xun Jin, Hyunggee Kim
Cullin3 E3 ubiquitin ligase ubiquitinates a wide range of substrates through substrate-specific adaptors Bric-a-brac, Tramtrack, and Broad complex (BTB) domain proteins. These E3 ubiquitin ligase complexes are involved in diverse cellular functions. Our recent study demonstrated that decreased Cullin3 expression induces glioma initiation and correlates with poor prognosis of patients with malignant glioma. However, the substrate recognition mechanism associated with tumorigenesis is not completely understood...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28059436/the-bet-bromodomain-inhibitor-jq1-suppresses-chondrosarcoma-cell-growth-via-regulation-of-yap-p21-c-myc-signaling
#17
Huan-Tian Zhang, Tao Gui, Yuan Sang, Jie Yang, Yu-Hang Li, Gui-Hong Liang, Thomas Li, Qing-Yu He, Zhen-Gang Zha
Chondrosarcoma, the second-most frequent primary bone malignancy, is generally more resistant to conventional chemotherapy and radiotherapy. Therefore, the development of an effective adjuvant therapy is necessary. Recently, targeting the epigenetic regulator such as bromodomain and extraterminal domain (BET) proteins has achieved great success. For instance, the bromodomain inhibitor JQ1 has been shown to inhibit the growth of several cancer cells both in vitro and in vivo. Herein we demonstrated that JQ1 significantly inhibited chondrosarcoma cell growth and colony formation...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28057768/tert-biology-and-function-in-cancer-beyond-immortalization
#18
Ana Pestana, João Vinagre, M Sobrinho-Simões, P Soares
Evasion of replicative senescence and proliferation without restriction, sometimes designated as immortalization, is one of cancer hallmarks that may be attained through reactivation of telomerase in somatic cells. In contrast to most normal cells in which there is lack of telomerase activity, upregulation of TERT transcription/activity is detected in 80 to 90% of malignant tumours. In several types of cancer there is a relationship between the presence of TERTp mutations, TERT mRNA expression and clinico-pathological features but the biological bridge between the occurrence of TERTp mutations and the aggressive/invasive features displayed by the tumours remains unidentified...
January 5, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28054503/inhibition-of-telomerase-using-bibr1532-enhances-doxorubicin-induced-apoptosis-in-pre-b-acute-lymphoblastic-leukemia-cells
#19
Davood Bashash, Mohadeseh Zareii, Ava Safaroghli-Azar, Mir Davood Omrani, Seyed H Ghaffari
OBJECTIVES: Interest into targeting telomerase in cancer has increased by the recent disclosure that elevated telomerase activity is associated with disease recurrence and poor outcome in cancers. In addition, cellular acquisition of unlimited replicative potential, which is closely related to the maintenance of telomeres mostly via the reactivation of telomerase, has been shown to confer loss of sensitivity to a wide range of anti-neoplastic agents. METHODS: To evaluate whether telomerase inhibition using non-nucleosidic inhibitor of telomerase BIBR1532 could enhance cytotoxic effect of doxorubicin in acute lymphoblastic leukemia, Nalm-6 pre-B ALL cells were subjected to combination treatment and subsequent cell viability, growth kinetics, caspase-3 activity, and transcriptional alteration of p73, p21, FOXO3a, c-Myc, hTERT, and other apoptosis-related target genes were investigated...
January 5, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28053540/a-novel-synthetic-asiatic-acid-derivative-induces-apoptosis-and-inhibits-proliferation-and-mobility-of-gastric-cancer-cells-by-suppressing-stat3-signaling-pathway
#20
Gang Wang, Yue Jing, Lingsen Cao, Changchang Gong, Zhunan Gong, Xiangrong Cao
Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells...
2017: OncoTargets and Therapy
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