Article
Oncology
Gregory M. Kelly, Fares Al-Ejeh, Robert McCuaig, Francesco Casciello, Nabilah Ahmad Kamal, Blake Ferguson, Antonia L. Pritchard, Sayed Ali, Ines P. Silva, James S. Wilmott, Georgina Long, Richard A. Scolyer, Sudha Rao, Nicholas K. Hayward, Frank Gannon, Jason S. Lee
Summary: The study suggests that LC3B may serve as a biomarker for checkpoint inhibitor blockade to guide patient selection. Additionally, G9a inhibition shows potential in enhancing the efficacy of checkpoint inhibitor blockade and increasing response rates in melanoma patients undergoing immunotherapy.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Anna Sannino, Maria Rosaria Scarfi, Melody Dufossee, Stefania Romeo, Loredana Poeta, Valerie Prouzet-Mauleon, Muriel Priault, Olga Zeni
Summary: Recent studies have shown that radiofrequency (RF) can reduce DNA damage induced by chemical or physical agents, similar to the adaptive response observed in radiobiology. This effect has been reported in vitro and in vivo, and possible cellular mechanisms activated by RF pre-exposure include perturbation of the cell redox status, DNA repair mechanisms, and stress response machinery. This study found that autophagy contributes to the RF-induced adaptive response in human neuroblastoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Barbara Kunzler Souza, Natalia Hogetop Freire, Thiago Santos Monteiro, Alice Laschuk Herlinger, Mariane Jaeger, Matheus G. S. Dalmolin, Caroline Brunetto de Farias, Lauro Gregianin, Andre T. Brunetto, Algemir L. Brunetto, Carol J. Thiele, Rafael Roesler
Summary: This study found that higher expression of G9a and GLP is associated with poorer prognosis and shorter overall survival in neuroblastoma and Ewing sarcoma. Pharmacological inhibition of G9a/GLP reduced the viability of tumor cells. The findings suggest that G9a and GLP may serve as potential epigenetic targets for pediatric solid cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Anna Montanaro, Samuel Kitara, Elisa Cerretani, Matteo Marchesini, Chiara Rompietti, Luca Pagliaro, Andrea Gherli, Angela Su, Maria Laura Minchillo, Mariafrancesca Caputi, Rodanthi Fioretzaki, Bruno Lorusso, Linda Ross, Gabriela Alexe, Elena Masselli, Marina Marozzi, Federica Maria Angela Rizzi, Roberta La Starza, Cristina Mecucci, Yan Xiong, Jian Jin, Angela Falco, Birgit Knoechel, Franco Aversa, Olivia Candini, Federico Quaini, Paolo Sportoletti, Kimberly Stegmaier, Giovanni Roti
Summary: Genomic studies have identified potential therapeutic targets in acute lymphoblastic leukemia (ALL) by analyzing genes involved in DNA methylation and histone modifications. This study focused on G9a/EHMT2 as a potential target in T-ALL and validated its role through various experiments. Mechanistically, G9a repression was found to influence lysosomal biogenesis and autophagic degradation, suggesting that epigenetic control plays a role in glycolytic dependent pathways in T-ALL.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Xixi Zeng, Anbang Sun, Weiyi Cheng, Xin Hou, Min Zhu, Yanhong Liao
Summary: Diabetic nephropathy (DN) is a renal complication caused by diabetes mellitus. This study investigated the role of STIM1 in the proliferation and fibrosis of HBZY-1 cells induced by high glucose (HG). The results showed that downregulation of STIM1 suppressed hyperglycemic cell proliferation and fibrosis by activating autophagy via the PI3K/AKT/mTOR signal pathway, providing a new target for DN treatment.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Oncology
Lina Wang, Jun Chen, Qianfei Zuo, Chunmei Wu, Ting Yu, Pengfei Zheng, Hui Huang, Jun Deng, Lichao Fang, Huamin Liu, Chenghong Li, Peiwu Yu, Quanming Zou, Junsong Zheng
Summary: The latest study reveals the high expression of calreticulin (CALR) in gastric cancer (GC) tissues, which is associated with lymph node metastasis and poor prognosis. The introduction of CALR enhances GC cell migration, while its repression has the opposite effects. CALR regulates the expression of epithelial-mesenchymal transition (EMT) markers and cellular adhesive molecules. Mechanistically, CALR mediates DNA methylation of E-cadherin promoter by interacting with G9a, thereby influencing GC cell migration.
Article
Multidisciplinary Sciences
Anne Meldgaard Hansen, Ying Ge, Mikkel Bruhn Schuster, Sachin Pundhir, Janus Schou Jakobsen, Adrija Kalvisa, Marta Cecylia Tapia, Sandra Gordon, Francesca Ambri, Frederik Otzen Bagger, Deo Pandey, Kristian Helin, Bo Torben Porse
Summary: The study reveals that H3K9me2 is crucial for the proliferation of AML and its loss leads to activation of the interferon pathway. Mechanistically, destabilization of a complex involving SUV39H1, G9A, and GLP is responsible for this activation.
Article
Oncology
Nanjing Liu, Chunmei Yang, Li Yang, Ting Li, Maoyuan Gong, Haobiao Wang, Jun Zhang, Hui Zhao, Lin Zou, Xiaoyan He
Summary: This study found that matrine has antiproliferative activity in NB cells by triggering autophagy through blocking the AKT-mTOR signaling pathway. In vivo experiments confirmed that matrine can inhibit NB tumor growth by altering phosphorylation levels and promoting autophagy. Therefore, matrine may be a potential therapeutic agent for treating NB.
Article
Oncology
Francesco Casciello, Gregory M. Kelly, Priya Ramarao-Milne, Nabilah Kamal, Teneale A. Stewart, Pamela Mukhopadhyay, Stephen H. Kazakoff, Mariska Miranda, Dorim Kim, Felicity M. Davis, Nicholas K. Hayward, Paula M. Vertino, Nicola Waddell, Frank Gannon, Jason S. Lee
Summary: G9a and EZH2, two histone methyltransferases commonly upregulated in several cancer types, cooperatively repress molecular pathways responsible for tumor cell death, and their simultaneous inhibition can induce tumor cell death.
Article
Chemistry, Multidisciplinary
Tae Woo Kim
Summary: CA induces cell death in gastric cancer cells through ER stress and Ca2+ release, and inhibiting ER stress can mitigate the cytotoxicity of CA. CA also triggers autophagic cell death by inhibiting G9a and activating LC3B.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Multidisciplinary Sciences
Hongxiao Wang, Zijun Song, Enjun Xie, Junyi Chen, Biyao Tang, Fudi Wang, Junxia Min
Summary: The combination of inhibiting LSD1 and G9a effectively suppresses cell growth in esophageal squamous cell carcinoma and reduces tumor growth. Clinical studies have shown that LSD1 and G9a are upregulated in cancer tissues and are significantly associated with poor prognosis. Inhibiting LSD1 and G9a induces cell death through S-phase arrest and apoptosis, and cotargeting ER stress pathways enhances this effect.
Article
Cell Biology
Rindert Missiaen, Nicole M. Anderson, Laura C. Kim, Bailey Nance, Michelle Burrows, Nicolas Skuli, Madeleine Carens, Romain Riscal, An Steensels, Fuming Li, M. Celeste Simon
Summary: Hepatocellular carcinoma (HCC) depends on exogenous arginine due to repression of urea cycle gene expression and unique dependence on cationic amino acid transporter SLC7A1. Arginine deprivation induces an integrated stress response, leading to HCC cell-cycle arrest and quiescence. Inhibiting GCN2 in arginine-deprived HCC cells promotes a senescent phenotype, making these cells vulnerable to senolytic compounds. Combined dietary arginine deprivation, GCN2 inhibition, and senotherapy show potential for HCC treatment.
Article
Cell Biology
Alin Garcia-Miranda, Karen Aylin Solano-Alcala, Jose Benito Montes-Alvarado, Arely Rosas-Cruz, Julio Reyes-Leyva, Napoleon Navarro-Tito, Paola Maycotte, Eduardo Castaneda-Saucedo
Summary: Autophagy is an intracellular recycling process that can be induced by leptin, a pro-tumorigenic protein, in cancer cell lines. Inhibition of autophagy reduces leptin-induced cell proliferation, migration, and ERK activation. This suggests a potential use for autophagy inhibition in breast cancer associated with obesity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiangdong Tian, Yuchao He, Lisha Qi, Dongming Liu, Dejun Zhou, Yun Liu, Wenchen Gong, Zhiqiang Han, Yuren Xia, Hua Li, Jiefu Wang, Kangwei Zhu, Lu Chen, Hua Guo, Qiang Zhao
Summary: Dormant cancer cells in colorectal cancer (CRC) have negative effects on prognosis, leading to cancer recurrence, metastasis, and drug resistance. A recent study revealed that autophagy plays a crucial role in the survival of dormant tumor cells. In this study, the researchers found that downregulation of polo-like kinases 4 (PLK4) induced dormancy and inhibited migration and invasion in CRC cell lines. They also discovered a correlation between PLK4 expression and dormancy markers in clinical samples. Mechanistically, downregulation of PLK4 induced autophagy through the MAPK signaling pathway, contributing to the restoration of aggressive tumor cells to a dormant state.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Oncology
Chin-Mu Hsu, Kung-Chao Chang, Tzer-Ming Chuang, Man-Ling Chu, Pei-Wen Lin, Hsiao-Sheng Liu, Shih-Yu Kao, Yi-Chang Liu, Chien-Tzu Huang, Min-Hong Wang, Tsung-Jang Yeh, Yuh-Ching Gau, Jeng-Shiun Du, Hui-Ching Wang, Shih-Feng Cho, Chi-En Hsiao, Yuhsin Tsai, Samuel Yien Hsiao, Li-Chuan Hung, Chia-Hung Yen, Hui-Hua Hsiao
Summary: This study identified G9a as an oncogenic marker in DLBCL and explored the potential of niclosamide as a treatment. The results showed that niclosamide effectively suppressed G9a expression, regulated autophagy-related gene expression, and inhibited DLBCL cell proliferation. The analysis of clinical specimens revealed that G9a protein levels correlated with DLBCL staging, suggesting its potential as a prognostic biomarker.
