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Autophagy and cancer

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https://www.readbyqxmd.com/read/29909423/prucalopride-inhibits-proliferation-of-ovarian-cancer-cells-via-phosphatidylinositol-3-kinase-pi3k-signaling-pathway
#1
Xiaolin Liu, Yintao Xu, Lu Zhang, Ting Liu, Hui Zhang
BACKGROUND Ovarian cancer is the second most common malignant tumor of the female reproductive system and is the leading cause of death of gynecological malignancies, but at present there is no effective and safe therapy. There is no previously published report on the anti-cancer effect of prucalopride, which is a high-affinity 5-HT4 receptor. The aim of the present study was to determine whether prucalopride can inhibit proliferation of ovarian cancer cells. MATERIAL AND METHODS The cell viability was detected by use of the Cell Counting Kit-8 (CCK-8) assay...
June 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29908094/ampk-dependent-mtor-pathway-is-involved-in-flavokawain-b-induced-autophagy-in-thyroid-cancer-cells
#2
Qin He, Wenping Liu, Sha Sha, Shanshan Fan, Yajing Yu, Li Chen, Ming Dong
Flavokawain B (FKB), a naturalkava chalcone, displays potent anti-tumor activity in various types of cancer, though the mechanism of action remains unclear. In this study, we report that FKB has profound effects on the metabolic state of human thyroid cancer (TCa) cells, leading to high autophagy flux via upregulation of AMPK, which in turn inhibits mTOR and activates Beclin-1 in TCa cells. We further demonstrate that the autophagy induced by FKB plays a pro-survival role in TCa cells both in vitro and in vivo...
June 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29907137/expression-of-the-glucagon-like-peptide-1-receptor-and-its-role-in-regulating-autophagy-in-endometrial-cancer
#3
Ranka Kanda, Haruko Hiraike, Osamu Wada-Hiraike, Takayuki Ichinose, Kazunori Nagasaka, Yuko Sasajima, Eiji Ryo, Tomoyuki Fujii, Yutaka Osuga, Takuya Ayabe
BACKGROUND: A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. However, the pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. Here, we investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients. METHODS: Human Ishikawa endometrial cancer cells were treated with different concentrations of liraglutide...
June 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29904891/%C3%AE-viniferin-activates-autophagic-apoptosis-and-cell-death-by-reducing-glucocorticoid-receptor-expression-in-castration-resistant-prostate-cancer-cells
#4
Kejun Cheng, Xi Liu, Lu Chen, Jian-Min Lv, Fa-Jun Qu, Xiu-Wu Pan, Lin Li, Xin-Gang Cui, Yi Gao, Dan-Feng Xu
Prostate cancer (PCa) is one of the most commonly diagnosed urological malignancies. However, there are limited therapies for PCa patients who develop biochemical recurrence after androgen deprivation therapy (ADT). In the present study, we investigated the therapeutic efficacy and mechanism of α-Viniferin (KCV), an oligostilbene of trimeric resveratrol, against human PCa cells and found that it markedly inhibited the proliferation of LNCaP, DU145, and PC-3 cancer cells in a time- and dose-dependent manner, and had a strong cytotoxicity in non-androgen-dependent PCa cells...
June 15, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29904125/deregulation-of-ube2c-mediated-autophagy-repression-aggravates-nsclc-progression
#5
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
https://www.readbyqxmd.com/read/29903018/emerging-roles-and-regulation-of-mit-tfe-transcriptional-factors
#6
REVIEW
Min Yang, En Liu, Li Tang, Yuanyuan Lei, Xuemei Sun, Jiaxi Hu, Hui Dong, Shi-Ming Yang, Mingfa Gao, Bo Tang
The MiT/TFE transcription factors play a pivotal role in the regulation of autophagy and lysosomal biogenesis. The subcellular localization and activity of MiT/TFE proteins are primarily regulated through phosphorylation. And the phosphorylated protein is retained in the cytoplasm and subsequently translocates to the nucleus upon dephosphorylation, where it stimulates the expression of hundreds of genes, leading to lysosomal biogenesis and autophagy induction. The transcription factor-mediated lysosome-to-nucleus signaling can be directly controlled by several signaling molecules involved in the mTORC1, PKC, and AKT pathways...
June 15, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29902340/autophagy-inhibition-synergizes-with-calcium-mobilization-to-achieve-efficient-therapy-of-malignant-gliomas
#7
Ha Thi Vu, Masahiko Kobayashi, Ahmed M Hegazy, Yuko Tadokoro, Masaya Ueno, Atsuko Kasahara, Yusuke Takase, Naho Nomura, Hui Peng, Chiaki Ito, Yasushi Ino, Tomoki Todo, Mitsutoshi Nakada, Atsushi Hirao
Autophagy plays a critical role in tumorigenesis, but how autophagy contributes to cancer cells' responses to chemotherapeutics remains controversial. To investigate the roles of autophagy in malignant gliomas, we used CRISPR/CAS9 to knock out the ATG5 gene, which is essential for autophagosome formation, in tumor cells derived from glioblastoma patients. While ATG5 disruption inhibited autophagy, it did not change the phenotypes of glioma cells and did not alter their sensitivity to temozolomide, an agent used for glioblastoma patient therapy...
June 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/29901268/integrative-analysis-of-proteome-and-ubiquitylome-reveals-unique-features-of-lysosomal-and-endocytic-pathways-in-gefitinib-resistant-non-small-cell-lung-cancer-cells
#8
Wang Li, Heyong Wang, Yan Yang, Tian Zhao, Zhixiong Zhang, Ye Tian, Zhaomie Shi, Xiaojun Peng, Fei Li, Yonghong Feng, Lei Zhang, Gening Jiang, Fan Zhang
Non-small cell lung cancer (NSCLC) patients carrying EGFR activating mutations treated with gefitinib, a tyrosine kinase inhibitor, will develop drug resistance. Ubiquitylation is one of major posttranslational modifications of proteins affecting the stability or function of proteins. However, the role of protein ubiquitylation in gefitinib resistance is poorly understood. To systematically identify the global change in protein expression and ubiquitylation during gefitinib resistance, we carried out quantitative global proteome and ubiquitylome study in a pair of gefitinib resistant and sensitive NSCLC cells...
June 14, 2018: Proteomics
https://www.readbyqxmd.com/read/29901165/-corrigendum-lsd1-negatively-regulates-autophagy-through-the-mtor-signaling-pathway-in-ovarian-cancer-cells
#9
Ye Wei, Tiantian Han, Ranran Wang, Jing Wei, Ke Peng, Qiong Lin, Genbao Shao
Subsequently to the publication of the article, the authors have realized that the bar chart that accompanied Fig. 4C, indicating the quantification of the western blotting data in this figure part, was published in the absence of either of the axes labels. The authors apologize for this oversight, and a corrected version of Fig. 4, which incorporates the missing labels, is shown opposite. The omission of these axes labels did not have an impact on the overall meaning of the paper. The authors regret that an incomplete version of Fig...
June 14, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29901098/artesunate-induces-apoptosis-and-autophagy-in-hct116-colon-cancer-cells-and-autophagy-inhibition-enhances-the-artesunate%C3%A2-induced-apoptosis
#10
Feng Jiang, Jin-Yong Zhou, Dan Zhang, Ming-Hao Liu, Yu-Gen Chen
The present study assessed the antitumor effect of artesunate (ART) in vitro and in vivo, as well as its underlying mechanism of action in HCT116 colon cancer cells. An MTT assay, DAPI staining, flow cytometry, western blotting, immunohistochemistry, transmission electron microscopy and TUNEL assay were performed to study the molecular mechanism underlying the antitumor effects of ART in HCT116 colon cancer cells. ART was observed to inhibit proliferation by inducing the apoptosis of HCT116 cells both in vitro and in vivo...
June 1, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29899823/metformin-exerts-antitumor-activity-via-induction-of-multiple-death-pathways-in-tumor-cells-and-activation-of-a-protective-immune-response
#11
Felipe V Pereira, Amanda Campelo L Melo, Jun Siong Low, Íris Arantes de Castro, Tárcio T Braga, Danilo C Almeida, Ana Gabriela U Batista de Lima, Meire I Hiyane, Matheus Correa-Costa, Vinicius Andrade-Oliveira, Clarice S T Origassa, Rosana M Pereira, Susan M Kaech, Elaine G Rodrigues, Niels Olsen S Câmara
The antitumor effect of metformin has been demonstrated in several types of cancer; however, the mechanisms involved are incompletely understood. In this study, we showed that metformin acts directly on melanoma cells as well as on the tumor microenvironment, particularly in the context of the immune response. In vitro , metformin induces a complex interplay between apoptosis and autophagy in melanoma cells. The anti-metastatic activity of metformin in vivo was assessed in several mouse models challenged with B16F10 cells...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899555/magnolin-promotes-autophagy-and-cell-cycle-arrest-via-blocking-lif-stat3-mcl-1-axis-in-human-colorectal-cancers
#12
Haiyang Yu, Shuangshuang Yin, Shiyue Zhou, Yingying Shao, Jiachen Sun, Xu Pang, Lifeng Han, Yi Zhang, Xiumei Gao, Chengyun Jin, Yuling Qiu, Tao Wang
Magnolin is a multi-bioactive natural compound that possesses underlying anti-cancer properties. However, the mechanisms underlying remain to be elucidated. Here, we report the role of magnolin in suppressing human colorectal cancer (CRC) cells via activating autophagy and cell cycle arrest in vitro and in vivo. Pre-treatment of cells with specific autophagy inhibitor (3-methyladenine) or knockdown of endogenous LC-3B by siRNA significantly abrogates magnolin-induced cell cycle arrest. Molecular validation mechanistically shows that magnolin-induced autophagy and cell cycle arrest in CRC cells is correlated with decreased transcriptional levels of leukemia inhibitory factor (LIF), and we further find that inhibition of LIF decreases phosphorylation level of Stat3 and represses transcriptional expression of Mcl-1...
June 13, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29899383/strong-and-sustained-activation-of-the-anticipatory-unfolded-protein-response-induces-necrotic-cell-death
#13
Mara Livezey, Rui Huang, Paul J Hergenrother, David J Shapiro
The endoplasmic reticulum stress sensor, the unfolded protein response (UPR), regulates intracellular protein homeostasis. While transient activation of the reactive UPR by unfolded protein is protective, prolonged and sustained activation of the reactive UPR triggers CHOP-mediated apoptosis. In the recently characterized, evolutionarily conserved anticipatory UPR, mitogenic hormones and other effectors pre-activate the UPR; how strong and sustained activation of the anticipatory UPR induces cell death was unknown...
June 13, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29899208/chrysin-attenuates-cell-viability-of-human-colorectal-cancer-cells-through-autophagy-induction-unlike-5-fluorouracil-oxaliplatin
#14
Yueh-Ming Lin, Chih-I Chen, Yi-Ping Hsiang, Yung-Chia Hsu, Kung-Chuan Cheng, Pei-Hsuan Chien, Hsiao-Lin Pan, Chien-Chang Lu, Yun-Ju Chen
Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear...
June 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29898994/flightless-i-blocks-p62-mediated-recognition-of-lc3-to-impede-selective-autophagy-and-promote-breast-cancer-progression
#15
Jian-Ping He, Pei-Pei Hou, Qi-Tao Chen, Wei-Jia Wang, Xiao-Yu Sun, Peng-Bo Yang, Ying-Ping Li, Lu-Ming Yao, Xiaotong Li, Xin-Dong Jiang, Kun-Yi Chien, Zhi-Ming Zhang, Qiu-Wan Wu, Allison J Cowin, Qiao Wu, Hang-Zi Chen
p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, the regulatory mechanism(s) behind this process and its association with breast cancer remain to be elucidated. Here we report that Flightless-I (FliI), a novel p62-interacting protein, promotes breast cancer progression by impeding selective autophagy. FliI was highly expressed in clinical breast cancer samples, and heterozygous deletion of FliI retarded development of mammary tumors in PyVT mice...
June 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29898430/mir-338-modulates-proliferation-and-autophagy-by-pi3k-akt-mtor-signaling-pathway-in-cervical-cancer
#16
Rong Lu, Zhanhua Yang, Guoying Xu, Shengsheng Yu
Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Given that autophagy is an important factor promoting tumor progression, we aim to investigate the functional role of miR-338 in autophagy and proliferation of cervical cancer. In our study, expression of miR-338 was validated by quantitative RT-PCR in 30 paired cervical cancer tissues and normal tissues. We performed MTT, colony formation and cell cycle assay to explore the effect of miR-338 on cell proliferation...
June 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29897944/a-specific-expression-profile-of-lc3b-and-p62-is-associated-with-nonresponse-to-neoadjuvant-chemotherapy-in-esophageal-adenocarcinomas
#17
Olivia Adams, Félice A Janser, Bastian Dislich, Sabina Berezowska, Magali Humbert, Christian A Seiler, Dino Kroell, Julia Slotta-Huspenina, Marcus Feith, Katja Ott, Mario P Tschan, Rupert Langer
Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resistance. We aimed to assess the impact of autophagy on chemotherapy response in EAC, with a special focus on paclitaxel. Responsiveness of EAC cell lines, OE19, FLO-1, OE33 and SK-GT-4, to paclitaxel was assessed using Alamar Blue assays...
2018: PloS One
https://www.readbyqxmd.com/read/29895332/long-noncoding-rna-hulc-accelerates-liver-cancer-by-inhibiting-pten-via-autophagy-cooperation-to-mir15a
#18
Xiaoru Xin, Mengying Wu, Qiuyu Meng, Chen Wang, Yanan Lu, Yuxin Yang, Xiaonan Li, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Jiao Li, Song Jia, Dongdong Lu
BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. RESULTS: HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer...
June 12, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29894707/silencing-pfkp-inhibits-starvation-induced-autophagy-glycolysis-and-epithelial-mesenchymal-transition-in-oral-squamous-cell-carcinoma
#19
Guanhui Chen, Haichao Liu, Yadong Zhang, Jianfeng Liang, Yue Zhu, Ming Zhang, Dongsheng Yu, Cheng Wang, Jinsong Hou
The tumor starvation microenvironment plays a pivotal role in the malignant progression of cancer, which is closely related to autophagy, glycolysis, and epithelial mesenchymal transition (EMT). Nevertheless, the underlying mechanisms of the starvation-mediated malignant phenotype are still not well documented. In this study, we aimed to investigate the effect of starvation on glycolysis, autophagy, and EMT in OSCC and to further elucidate the key metabolic modulator. The results showed that starvation can induce autophagy, EMT, and enhanced glycolysis in OSCC cells...
June 9, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29891531/autophagy-in-cancer-a-complex-relationship
#20
REVIEW
Lindsay Wilde, Katherina Tanson, Joseph Curry, Ubaldo Martinez-Outschoorn
Macroautophagy is the process by which cells package and degrade cytosolic components, and recycle the breakdown products for future use. Since its initial description by Christian de Duve in the 1960s, significant progress has been made in understanding the mechanisms that underlie this vital cellular process and its specificity. Furthermore, macroautophagy is linked to pathologic conditions such as cancer and is being studied as a therapeutic target. In this review, we will explore the connections between autophagy and cancer, which are tumor- and context-dependent and include the tumor microenvironment...
June 11, 2018: Biochemical Journal
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