Article
Oncology
Vitaliy O. Kaminskyy, Petra Haag, Metka Novak, Akos Vegvari, Vasiliki Arapi, Rolf Lewensohn, Kristina Viktorsson
Summary: This study investigates the role of Ephrin type-A receptor 2 (EphA2) in DNA damage response signaling and cellular effects of ionizing radiation (IR) in NSCLC cells. Silencing EphA2 sensitizes cells to IR, leading to increased caspase-3 activation, PARP-1 cleavage, and reduced clonogenic survival. EphA2 interacts with DNA-PKcs in the cell nucleus, suggesting a novel mechanism involving EphA2 in DDR signaling and IR responsiveness.
Article
Biochemistry & Molecular Biology
Aashish Soni, Xiaolu Duan, Martin Stuschke, George Iliakis
Summary: The activation of the intra-S-phase checkpoint is essential for maintaining genomic stability and involves the activities of ATM and ATR. DNA-PKcs also contributes to the recovery from the checkpoint. The organization of the intra-S-phase checkpoint is similar to that of the G(2) checkpoint.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Fanghua Li, Emil Mladenov, Rositsa Dueva, Martin Stuschke, Beate Timmermann, George Iliakis
Summary: The current understanding of the involvement of PI3-kinases in checkpoint responses after DNA damage reveals that ATM is the key regulator of G(1), S, or G(2)-phase checkpoints, ATR is only partly involved in the regulation of S and G(2)-phase checkpoints, and DNA-PKcs is not involved in checkpoint regulation. However, recent studies have shown complex integrations and interactions among ATM, ATR, and DNA-PKcs in checkpoint responses to ionizing radiation (IR), depending on the cell cycle phase and the load of DNA double-strand breaks (DSBs). These findings highlight the importance of these kinases in optimizing DSB processing.
Article
Oncology
Hao Hu, Wuqiang Chen, Shuo Zhang, Yuzheng Xue, Youzhao He, Yuanlong Gu
Summary: The study revealed that the upregulation of DNA-PKcs in PDAC cells is promoted by NEAT1 and miR-101, leading to the malignant behaviors of the cells. NEAT1 functions as an oncogene influencing cell proliferation, migration, and invasion.
Article
Cell Biology
Lan Yu, Yue Lang, Jiaming Guo, Jianming Cai, Zeng-Fu Shang, Benjamin P. C. Chen
Summary: Combining targeted therapeutic agents like DNA-PKcs and HDACs inhibitors shows potential in cancer treatment by enhancing cancer cell sensitivity to treatment and inducing mitotic arrest followed by apoptotic cell death. The crosstalk between DNA-PKcs and HDACs signaling pathways highlights the promise of combined targeting strategies in cancer therapy.
Article
Medicine, Research & Experimental
Thom G. A. Reuvers, Nicole S. Verkaik, Debra Stuurman, Corrina de Ridder, Marian C. Clahsen-van Groningen, Erik de Blois, Julie Nonnekens
Summary: Peptide receptor radionuclide therapy (PRRT) can improve the progression-free survival and quality of life of neuroendocrine tumor (NET) patients, but complete cures are rare and dose-limiting toxicity has been reported. PRRT induces DNA damage, with DNA double strand breaks (DSBs) being the most cytotoxic. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is involved in DSB repair and inhibiting it can potentially enhance PRRT efficacy without increasing the dosage.
Article
Cell Biology
Hao Gu, Jian Li, Rongrong Zhang
Summary: Melatonin was found to inhibit endothelial cell apoptosis under oxidative stress induced by H2O2 through modulation of the miR-101/DNA-PKcs/PI3K/AKT signaling pathway.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Joelle Al-Choboq, Melanie L. Ferlazzo, Laurene Sonzogni, Adeline Granzotto, Laura El-Nachef, Mira Maalouf, Elise Berthel, Nicolas Foray
Summary: Usher syndrome is a rare genetic disease characterized by hearing loss, visual impairment, and vestibular dysfunctions. This study provides the first radiobiological characterization of cells from USH1 patients at both molecular and cellular levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Laura El-Nachef, Joelle Al-Choboq, Juliette Restier-Verlet, Adeline Granzotto, Elise Berthel, Laurene Sonzogni, Melanie L. Ferlazzo, Audrey Bouchet, Pierre Leblond, Patrick Combemale, Stephane Pinson, Michel Bourguignon, Nicolas Foray
Summary: The individual response to ionizing radiation (IR) raises various medical, scientific, and societal concerns. From the 1930s, there has been confusion in the literature regarding the term radiosensitivity, which has been used interchangeably to describe the toxic, cancerous, or aging effects of IR. Differences in mechanisms causing predisposition to radiation-induced adverse tissue reactions (radiosensitivity) and cancer (radiosusceptibility) have been observed, with ATM protein playing a potential role in classifying genetic syndromes associated with radiosensitivity and radiosusceptibility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Huaping Xiao, Fanghua Li, Emil Mladenov, Aashish Soni, Veronika Mladenova, Bing Pan, Rositsa Dueva, Martin Stuschke, Beate Timmermann, George Iliakis
Summary: The load of DNA double-strand breaks induced by ionizing radiation plays a key role in determining the repair pathway choice in higher eukaryotes. The integration of DNA-PKcs into resection regulation suggests a mechanism adaptively facilitating resection. Mutations in DNA-PKcs result in hyper-resection, ruling out the competition between c-NHEJ and HR as the cause of increased resection.
Article
Biochemistry & Molecular Biology
Margarita Pustovalova, Philipp Malakhov, Anastasia Guryanova, Maxim Sorokin, Maria Suntsova, Anton Buzdin, Andreyan N. N. Osipov, Sergey Leonov
Summary: Radioresistance is a major obstacle in the successful therapy of many cancers, including non-small cell lung cancer (NSCLC). By comparing the transcriptional changes of radioresistant NSCLC cells with parental cells using RNA-seq, differentially expressed genes associated with radioresistance were identified. These gene expressions reflect the complex biological processes involved in clinical cancer cell eradication and might serve as potential biomarkers and therapeutic targets for NSCLC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Kristina Bannik, Balazs Madas, Sabrina Jarke, Andreas Sutter, Gerhard Siemeister, Christoph Schatz, Dominik Mumberg, Sabine Zitzmann-Kolbe
Summary: This study aimed to investigate the effects of high LET alpha-radiation combined with DDR inhibitors and compare it with the radiosensitizing effect of low LET X-ray radiation. The results showed that the inhibitors sensitized different cancer cell lines to radiation, with sensitization enhancement ratios ranging from 1.6 to 1.85. ATMi preferentially sensitized cancer cells and normal HEK293 cells to alpha-radiation, while DNA-PKi and ATMi could sensitize cancer cells to X-ray depending on the cancer cell type.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Wei-Min Chen, Jui-Chung Chiang, Zengfu Shang, Guillermo Palchik, Ciara Newman, Yuanyuan Zhang, Anthony J. Davis, Hsinyu Lee, Benjamin P. C. Chen
Summary: DNA-PKcs plays a key role in DNA double-strand break repair and is involved in the cellular response to oxidative stress. It interacts with mitochondria proteins ANT2 and VDAC2 to maintain oxidative phosphorylation and mitochondrial membrane potential. The formation of the DAV complex is important for energizing the cell and its dissociation under oxidative stress helps reduce ROS production and promote cellular recovery.
Article
Cell Biology
Joelle Al-Choboq, Thibaud Mathis, Juliette Restier-Verlet, Laurene Sonzogni, Laura El Nachef, Adeline Granzotto, Michel Bourguignon, Nicolas Foray
Summary: The study of radiation-induced cataractogenesis is limited by the shortage of available epithelial lens cell lines and reliable biomarkers of aging caused by radiation. A mechanistic model, RIANS, has been developed based on the nucleoshuttling of the ATM protein, which suggests the formation of perinuclear ATM crowns as a potential biomarker of aging. The radiobiological characterization of human and porcine lens cell lines showed delayed RIANS and the overexpression of the BFSP2 protein, which interacts with ATM and may facilitate the formation of perinuclear ATM crowns.
Article
Dermatology
Vida Chitsazzadeh, Tran N. Nguyen, Alvaro de Mingo Pulido, Bruna B. Bittencourt, Lili Du, Charles H. Adelmann, Ivannie Ortiz Rivera, Kimberly A. Nguyen, Leah D. Guerra, Andrew Davis, Marco Napoli, Wencai Ma, Richard Eric Davis, Kimal Rajapakshe, Cristian Coarfa, Elsa R. Flores, Kenneth Y. Tsai
Summary: Upregulation of miR-181a promotes the development of cutaneous squamous cell carcinoma (cSCC) by targeting TGF beta R3, a component of TGF beta signaling. Overexpression of miR-181a or knockdown of TGF beta R3 significantly suppresses UV-induced apoptosis in HaCaT cells and normal human epidermal keratinocytes. Moreover, miR-181a overexpression or TGF beta R3 knockdown enhances the survival, migration, and invasion of tumor cells.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Oncology
Zhiming Zheng, Wooi Loon Ng, Xiangming Zhang, Jeffrey J. Olson, Chunhai Hao, Walter J. Curran, Ya Wang
Article
Oncology
Xiangming Zhang, Wooi-Loon Ng, Ping Wang, LinLin Tian, Erica Werner, Huichen Wang, Paul Doetsch, Ya Wang
Article
Oncology
Baocheng Hu, Xiaomin Ying, Jian Wang, Jittima Piriyapongsa, I. King Jordan, Jipo Sheng, Fang Yu, Po Zhao, Yazhuo Li, Hongyan Wang, Wooi Loon Ng, Shuofeng Hu, Xiang Wang, Chenguang Wang, Xiaofei Zheng, Wuju Li, Walter J. Curran, Ya Wang
Article
Genetics & Heredity
Wooi Loon Ng, Dan Yan, Xiangming Zhang, Yin-Yuan Mo, Ya Wang
Article
Multidisciplinary Sciences
Dan Yan, Wooi Loon Ng, Xiangming Zhang, Ping Wang, Zhaobin Zhang, Yin-Yuan Mo, Hui Mao, Chunhai Hao, Jeffrey J. Olson, Walter J. Curran, Ya Wang
Review
Biochemistry & Molecular Biology
Pedram Yadollahi, You-Kyoung Jeon, Wooi Loon Ng, Inhak Choi
Summary: In the past decade, cancer immunotherapies targeting PD-L1 and PD-1 pathway have achieved unprecedented clinical success. In addition to its immunological functions in tumor microenvironment, recent studies have revealed the non-immunological role of PD-L1 in regulating cancer intrinsic activities such as mesenchymal transition, metabolism, stemness, and autophagy.
Review
Oncology
Wooi-Loon Ng, Qian Huang, Xinjian Liu, Mary Zimmerman, Fang Li, Chuan-Yuan Li
TRANSLATIONAL CANCER RESEARCH
(2013)
Article
Biochemistry & Molecular Biology
EHJ Yew, NS Cheung, MS Choy, RZ Qi, AYW Lee, ZF Peng, AJ Melendez, J Manikandan, ESC Koay, LL Chiu, WL Ng, M Whiteman, J Kandiah, B Halliwell
JOURNAL OF NEUROCHEMISTRY
(2005)
Article
Microbiology
C Drosten, LL Chiu, M Panning, HN Leong, W Preiser, JS Tam, S Günther, S Kramme, P Emmerich, WL Ng, H Schmitz, ESC Koay
JOURNAL OF CLINICAL MICROBIOLOGY
(2004)