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Autophagy and radioresistance

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https://www.readbyqxmd.com/read/29694502/lncrna-hulc-mediates-radioresistance-via-autophagy-in-prostate-cancer-cells
#1
Changxuan Chen, Kaizhen Wang, Qian Wang, Xin Wang
Prostate cancer (PCa) is the second leading cause of cancer death in men. Irradiation is one of the available options for treatment of PCa, however, approximately 10-45% of PCa are resistant to irradiation. We aimed to explore the role of long non-coding RNA highly upregulated in liver cancer (HULC) in the sensitivity of PCa cells to irradiation. Survival rate, cell apoptosis, cycle, expressions of related proteins, and caspase-3 activity were assessed to explore the effects of HULC on sensitivity of PCa cells to irradiation...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29679028/radiosensitization-by-marine-sponge-agelas-sp-extracts-in-hepatocellular-carcinoma-cells-with-autophagy-induction
#2
Changhoon Choi, Arang Son, Hyi-Seung Lee, Yeon-Ju Lee, Hee Chul Park
Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-cancer drug discovery, but little is known regarding radiation therapy applications. In this study, six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29644941/role-of-micrornas-in-treatment-response-in-prostate-cancer
#3
Anshuli Razdan, Paul de Souza, Tara Laurie Roberts
Prostate cancer (PCa) is the most common non-skin cancer in men worldwide, resulting in significant mortality and morbidity. Depending on the grade and stage of the cancer, patients may be given radiation therapy, hormonal therapy, or chemotherapy. However, more than half these patients develop resistance to treatment, leading to disease progression and metastases, often with lethal consequences. MicroRNAs (miRNAs) are short, non-coding RNAs, which regulate numerous physiological as well as pathological processes, including cancer...
March 15, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29602802/smad4-gene-mutation-renders-pancreatic-cancer-resistance-to-radiotherapy-through-promotion-of-autophagy
#4
Feng Wang, Xiaojun Xia, Chunying Yang, Jianliang Shen, Junhua Mai, Han-Cheon Kim, Dickson Kirui, Ya'an Kang, Jason B Fleming, Eugene J Koay, Sankar Mitra, Mauro Ferrari, Haifa Shen
PURPOSE: Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy. EXPERIMENTAL DESIGN: We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance...
March 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29459645/inhibition-of-atg12-mediated-autophagy-by-mir-214-enhances-radiosensitivity-in-colorectal-cancer
#5
J L Hu, G Y He, X L Lan, Z C Zeng, J Guan, Y Ding, X L Qian, W T Liao, Y Q Ding, L Liang
Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase patients' response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot...
February 20, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29377763/egfrviii-expression-triggers-a-metabolic-dependency-and-therapeutic-vulnerability-sensitive-to-autophagy-inhibition
#6
Barry Jutten, Tom G Keulers, Hanneke J M Peeters, Marco B E Schaaf, Kim G M Savelkouls, Inge Compter, Ruud Clarijs, Olaf E M G Schijns, Linda Ackermans, Onno P M Teernstra, Marijke I Zonneveld, Resi M E Colaris, Ludwig Dubois, Marc A Vooijs, Johan Bussink, Julio Sotelo, Jan Theys, Guido Lammering, Kasper M A Rouschop
Expression of EGFRvIII is frequently observed in glioblastoma and is associated with increased cellular proliferation, enhanced tolerance to metabolic stresses, accelerated tumor growth, therapy resistance and poor prognosis. We observed that expression of EGFRvIII elevates the activation of macroautophagy/autophagy during starvation and hypoxia and explored the underlying mechanism and consequence. Autophagy was inhibited (genetically or pharmacologically) and its consequence for tolerance to metabolic stress and its therapeutic potential in (EGFRvIII+ ) glioblastoma was assessed in cellular systems, (patient derived) tumor xenopgrafts and glioblastoma patients...
2018: Autophagy
https://www.readbyqxmd.com/read/29232556/mst4-phosphorylation-of-atg4b-regulates-autophagic-activity-tumorigenicity-and-radioresistance-in-glioblastoma
#7
Tianzhi Huang, Chung Kwon Kim, Angel A Alvarez, Rajendra P Pangeni, Xuechao Wan, Xiao Song, Taiping Shi, Yongyong Yang, Namratha Sastry, Craig M Horbinski, Songjian Lu, Roger Stupp, John A Kessler, Ryo Nishikawa, Ichiro Nakano, Erik P Sulman, Xinghua Lu, Charles David James, Xiao-Ming Yin, Bo Hu, Shi-Yuan Cheng
ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232380/inhibition-of-grp78-abrogates-radioresistance-in-oropharyngeal-carcinoma-cells-after-egfr-inhibition-by-cetuximab
#8
Chaonan Sun, Chuyang Han, Yuanjun Jiang, Ning Han, Miao Zhang, Guang Li, Qiao Qiao
The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER) homeostatic state and result in ER stress (ERS), subsequently causing resistance to radiation and drugs...
2017: PloS One
https://www.readbyqxmd.com/read/28936522/a-novel-hif-1%C3%AE-vmp1-autophagic-pathway-induces-resistance-to-photodynamic-therapy-in-colon-cancer-cells
#9
M E Rodríguez, C Catrinacio, A Ropolo, V A Rivarola, M I Vaccaro
Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as an adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumors and leads to chemo/radioresistance. Recently, it has been shown that in response to hypoxia, cells can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment...
November 8, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28900507/targeting-micrornas-in-prostate-cancer-radiotherapy
#10
REVIEW
Jie Ni, Joseph Bucci, Lei Chang, David Malouf, Peter Graham, Yong Li
Radiotherapy is one of the most important treatment options for localized early-stage or advanced-stage prostate cancer (CaP). Radioresistance (relapse after radiotherapy) is a major challenge for the current radiotherapy. There is great interest in investigating mechanisms of radioresistance and developing novel treatment strategies to overcome radioresistance. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level, participating in numerous physiological and pathological processes including cancer invasion, progression, metastasis and therapeutic resistance...
2017: Theranostics
https://www.readbyqxmd.com/read/28656285/lkb1-promotes-radioresistance-in-esophageal-cancer-cells-exposed-to-radiation-by-suppression-of-apoptosis-and-activation-of-autophagy-via-the-ampk-pathway
#11
Qing He, Jing Li, Feng Dong, Chuanshu Cai, Xi Zou
Liver kinase B (LKB) 1 acts as a tumor suppressor in a broad spectrum of human cancers, and is important in chemoradiotherapy treatment of various tumor types. However, the potential function of LKB1 in esophageal cancer radiotherapy remains to be elucidated. The aim of the present study was to investigate the role of LKB1 in radiosensitivity of esophageal cancer in vivo and in vitro, and to explore its molecular mechanism. Eca‑109 cells transfected with LKB1 overexpression plasmid were xenografted into nude mice and subjected to irradiation and it was observed that the tumor volume was significantly increased in LKB1‑overexpressed tumors compared with that of the control tumors...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28642840/cytolethal-distending-toxin-enhances-radiosensitivity-in-prostate-cancer-cells-by-regulating-autophagy
#12
Hwai-Jeng Lin, Hsin-Ho Liu, Chia-Der Lin, Min-Chuan Kao, Yu-An Chen, Chuan Chiang-Ni, Zhi-Pei Jiang, Mei-Zi Huang, Chun-Jung Lin, U-Ging Lo, Li-Chiung Lin, Cheng-Kuo Lai, Ho Lin, Jer-Tsong Hsieh, Cheng-Hsun Chiu, Chih-Ho Lai
Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28570501/estrogen-receptor-mediates-the-radiosensitivity-of-triple-negative-breast-cancer-cells
#13
Xingxing Chen, Ningyi Ma, Zhirui Zhou, Ziliang Wang, Qunchao Hu, Jurui Luo, Xin Mei, Zhaozhi Yang, Li Zhang, Xiaofang Wang, Yan Feng, Xiaoli Yu, Jinli Ma, Xiaomao Guo
BACKGROUND This study aimed to evaluate differences in the radiosensitivities of triple-negative breast cancer (TNBC) and luminal-type breast cancer cells and to investigate the effects of estrogen receptor (ER) expression on the biological behaviors of the cells. MATERIAL AND METHODS Colony-forming assays were performed to detect differences in radiosensitivities in breast cancer cell lines. Gene transfection technology was used to introduce the expression of ERα in TNBC cells to compare the difference in radiosensitivity between the TNBC cells and ERα transfected cells...
June 1, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28463025/autophagy-enhanced-the-radioresistance-of-non-small-cell-lung-cancer-by-regulating-ros-level-under-hypoxia-condition
#14
Xiaoyan Chen, Ping Wang, Fei Guo, Xiangdong Wang, Juan Wang, Jinping Xu, Dexiao Yuan, Jianghong Zhang, Chunlin Shao
PURPOSE: Tumor resistance towards radiation has been a big obstacle in the poor prognosis of lung cancer. It has been reported that hypoxia and autophagy partly contribute to this resistance. However, there is controversy over whether autophagy plays a positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance. MATERIALS AND METHODS: A549 cells were treated with conditioned medium (CM) under 12 h hypoxia or normoxia before irradiation, followed by the measurement of clonogenic survival, reactive oxygen species (ROS), signal of mitochondria and autophagy flux...
August 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28431753/eef2k-promotes-progression-and-radioresistance-of-esophageal-squamous-cell-carcinoma
#15
Hongcheng Zhu, Hongmei Song, Guangzong Chen, Xi Yang, Jia Liu, Yangyang Ge, Jing Lu, Qin Qin, Chi Zhang, Liping Xu, Xiaoke Di, Jing Cai, Jianxin Ma, Shu Zhang, Xinchen Sun
OBJECTIVES: To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively...
September 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28428710/cma-down-regulates-p53-expression-through-degradation-of-hmgb1-protein-to-inhibit-irradiation-triggered-apoptosis-in-hepatocellular-carcinoma
#16
Jing-Hua Wu, Jia-Pei Guo, Jun Shi, Hui Wang, Lei-Lei Li, Bin Guo, Dian-Xing Liu, Qing Cao, Zhi-Yong Yuan
AIM: To investigate the mechanism of chaperone-mediated autophagy (CMA)-induced resistance to irradiation-triggered apoptosis through regulation of the p53 protein in hepatocellular carcinoma (HCC). METHODS: Firstly, we detected expression of lysosome-associated membrane protein 2a (Lamp-2a), which is the key protein of CMA, by western blot in HepG2 and SMMC7721 cells after irradiation. We further used shRNA Lamp-2a HCC cells to verify the radioresistance induced by CMA...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28342984/hdac4-and-hdac6-sustain-dna-double-strand-break-repair-and-stem-like-phenotype-by-promoting-radioresistance-in-glioblastoma-cells
#17
Francesco Marampon, Francesca Megiorni, Simona Camero, Clara Crescioli, Heather P McDowell, Roberta Sferra, Antonella Vetuschi, Simona Pompili, Luca Ventura, Francesca De Felice, Vincenzo Tombolini, Carlo Dominici, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina
The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery...
July 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28302031/hif1a-is-overexpressed-in-medulloblastoma-and-its-inhibition-reduces-proliferation-and-increases-epas1-and-atg16l1-methylation
#18
Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28216370/targeting-autophagy-in-cancer-stem-cells-as-an-anticancer-therapy
#19
REVIEW
Yuanyuan Lei, Dan Zhang, Jin Yu, Hui Dong, Jianwei Zhang, Shiming Yang
Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and metastasis. Autophagy, a process of cellular self-digestion and response to stress, has a role in tumor formation and progression, and it may play a dual role in CSCs-related resistance to anticancer therapy...
May 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28134935/egr-1-regulates-irradiation-induced-autophagy-through-atg4b-to-promote-radioresistance-in-hepatocellular-carcinoma-cells
#20
W-X Peng, Y-Y Wan, A-H Gong, L Ge, J Jin, M Xu, C-Y Wu
Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells...
January 30, 2017: Oncogenesis
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