Article
Medicine, Research & Experimental
Zongang Liu, Mengnan Zhao, Xizi Jiang, Yao Zhang, Suning Zhang, Yitong Xu, Hongjiu Ren, Hongbo Su, Huanxi Wang, Xueshan Qiu
Summary: This study elucidates the role of KLHL17 in the development and progression of NSCLC using clinical samples and NSCLC cell lines. The results show that upregulated KLHL17 in NSCLC promotes the proliferation and migration of tumor by activating Ras/MAPK signaling pathway, and suggest that KLHL17 may be a novel therapeutic target for the treatment of NSCLC.
LABORATORY INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Isshin Shiiba, Keisuke Takeda, Shun Nagashima, Naoki Ito, Takeshi Tokuyama, Shun-Ichi Yamashita, Tomotake Kanki, Toru Komatsu, Yasuteru Urano, Yuuta Fujikawa, Ryoko Inatome, Shigeru Yanagi
Summary: MITOL regulates Parkin-mediated cell death by promoting ubiquitination of Parkin at lysine 220 residue, leading to its proteasomal degradation and controlling mitophagy. Deletion of MITOL results in accumulation of active phosphorylated Parkin in the ER, causing FKBP38 degradation and increased cell death.
Article
Biochemistry & Molecular Biology
Yasaman Pakdaman, Siren Berland, Helene J. Bustad, Sigrid Erdal, Bryony A. Thompson, Paul A. James, Kjersti N. Power, Stale Ellingsen, Martin Krooni, Line I. Berge, Adrienne Sexton, Laurence A. Bindoff, Per M. Knappskog, Stefan Johansson, Ingvild Aukrust
Summary: Variants in STUB1 can cause both autosomal recessive SCAR16 and dominant SCA48, with novel dominantly inherited STUB1 variants in patients showing symptoms after 30 years of age, cerebellar atrophy, and cognitive/psychiatric phenotypes. Studies on the molecular properties of these dominant variants revealed impaired ubiquitin ligase activity and altered oligomerization properties of the CHIP, expanding the understanding of SCA48 and suggesting a need for re-evaluation of assumptions about unaffected carriers of recessive STUB1 variants in SCAR16 families. Further investigations are needed to verify the disease status of SCAR16 heterozygotes and elucidate the molecular relationship between SCA48 and SCAR16 diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yongjie Xu, Yumeng Hu, Tao Xu, Kaowen Yan, Ting Zhang, Qin Li, Fen Chang, Xueyuan Guo, Jingyu Peng, Mo Li, Min Zhao, Hongying Zhen, Luzheng Xu, Duo Zheng, Li Li, Genze Shao
Summary: The study reveals that RNF8 is overexpressed in lung cancer and promotes cancer cell proliferation and resistance to chemotherapy. Therefore, RNF8 could be a very promising target in precision medicine for lung cancer.
Article
Multidisciplinary Sciences
Wenshuai Wang, Benjamin Goette, Rong Guo, Anna Marie Pyle
Summary: The study shows that Riplet plays an essential role in RIG-I signaling, independent of RIG-I oligomerization on long dsRNA. By analyzing the structure of the complex, the molecular interfaces controlling Riplet-mediated activation are revealed, leading to the formulation of a unified model for the role of Riplet in signaling.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Fabienne Burger, Daniela Baptista, Aline Roth, Karim J. Brandt, Kapka Miteva
Summary: This study reveals the crucial role of Peli1 in atherosclerosis as an important regulator of inflammation and vascular smooth muscle cell phenotypic modulation, subsequently leading to atherosclerotic plaque destabilization.
Article
Biochemistry & Molecular Biology
Yanwei Lu, Xudong Li, Hongli Liu, Jun Xue, Zhen Zeng, Xiaorong Dong, Tao Zhang, Gang Wu, Kunyu Yang, Shuangbing Xu
Summary: LZTS2 is downregulated in HCC and associated with poor prognosis. It inhibits HCC tumorigenesis and metastasis by suppressing PI3K/AKT signaling. Furthermore, LZTS2 is targeted for degradation by E3 ligase and protein kinase, promoting HCC progression and metastasis.
Article
Biochemistry & Molecular Biology
Jiawei Xiong, Fabin Yang, Fan Wei, Feng Yang, Honghui Lin, Dawei Zhang
Summary: HLS1 plays a key role in the development of the apical hook in plants, and SIZ1 regulates the rapid opening of the apical hook by mediating HLS1 SUMOylation. The opening of the apical hook is associated with a decrease in SIZ1 transcript levels, leading to reduced HLS1 SUMOylation. In addition, HY5 promotes the rapid opening of the apical hook by inhibiting SIZ1 transcription.
Article
Oncology
Haiyun Wang, Qiuling Huang, Jianhong Xia, Shan Cheng, Duanqing Pei, Xiaofei Zhang, Xiaodong Shu
Summary: MIB1 overexpression is detected in lung squamous carcinoma and adenocarcinoma and negatively correlates with patient survival. MIB1 induces EMT and cell migration through the Notch pathway, and degrades NRF2 in a Notch-independent manner, disrupting cellular antioxidant capacity.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Kim Ghilarducci, Valerie C. Cabana, Camille Desroches, Kahina Chabi, Steve Bourgault, Laurent Cappadocia, Marc P. Lussier
Summary: Protein ubiquitination plays a role in various cellular functions beyond protein degradation. The study demonstrates the interaction between RNF167 and conjugating E2 enzymes, revealing submicromolar dissociation constants and providing insights into the mechanism of binding. Additionally, the research shows that GluA2 ubiquitination by UBE2N is possible only after priming by another conjugating E2 enzyme, shedding light on the ubiquitination process mediated by RNF167.
Article
Oncology
Jia-xin Chen, Da Xu, Jian-wei Cao, Li Zuo, Zhi-tao Han, Yi-jun Tian, Chuan-min Chu, Wang Zhou, Xiu-wu Pan, Xin-gang Cui
Summary: This study demonstrated the crucial role of TRIM47 in promoting malignant biological behavior in renal cell carcinoma, by interacting with P53 protein to increase its ubiquitination and degradation; The TRIM47-P53 axis might be a potential therapeutic target for RCC progression.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Hang Chen, Rui Yang, Lei Xing, Bin Wang, Dawei Liu, Xiaoqiang Ou, Yumei Deng, Rong Jiang, Junxia Chen
Summary: This study identified a novel hypoxia-induced circRNA, circPFKFB4, and demonstrated its role in promoting breast cancer progression. The study revealed an interaction between circPFKFB4 and the CRL4DDB2 E3 ubiquitin ligase and suggested circPFKFB4 as a potential biomarker and therapeutic target for breast cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Plant Sciences
Ling Wang, Xue Zhang, Ziyang Qu, Weichen Guo, Steve van Nocker, Chaohong Zhang
Summary: ERF transcription factor VviERF105 in grapevine plays a significant role in regulating plant growth, response to abiotic stresses, and interacts with VviPUB19 for degradation.
ENVIRONMENTAL AND EXPERIMENTAL BOTANY
(2022)
Article
Biochemistry & Molecular Biology
Fang Qi, Xin Zhang, Likun Wang, Caixia Ren, Xuyang Zhao, Jianyuan Luo, Dan Lu
Summary: In this study, the researchers discovered that NEURL3 serves as an E3 ubiquitin ligase for IRF7, playing a crucial role in the positive regulation of IRF7 in host antiviral immune signaling.
Article
Cell Biology
Jiansong Liu, Yichen Zang, Cunying Ma, Dandan Wang, Zhuangfei Tian, Xia Xu, Wenjuan Li, Jihui Jia, Zhifang Liu
Summary: This study reveals that STYX acts as an oncogene in gastric cancer (GC) by inhibiting the degradation function of FBXO31, and may serve as a potential therapeutic target and prognostic biomarker in GC. STYX's interaction with FBXO31 and its regulation by c-Jun and Helicobacter pylori are key mechanisms driving GC progression.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Vinee Purohit, Lidong Wang, Huibin Yang, Jiufeng Li, Gina M. Ney, Erica R. Gumkowski, Akash J. Vaidya, Annie Wang, Amit Bhardwaj, Ende Zhao, Igor Dolgalev, Andrea Zamperone, Ethan V. Abel, Marina Pasca Di Magliano, Howard C. Crawford, Daniel Diolaiti, Thales Y. Papagiannakopoulos, Costas A. Lyssiotis, Diane M. Simeone
Summary: The overexpression of ATDC in pancreatic cancer promotes tumor growth and metastasis by protecting cancer cells from ROS through stabilizing NRF2. This mechanism enhances chemoresistance and modulates redox balance in cancer cells.
GENES & DEVELOPMENT
(2021)
Editorial Material
Oncology
Rafael Winograd, Diane M. Simeone, Dafna Bar-Sagi
Summary: Immune checkpoint blockade has shown efficacy in multiple cancers, but further improvements are needed to increase response rates and achieve clinical efficacy in cold tumors. Mechanistic studies of tumor-specific immunosuppressive pathways can uncover biological barriers to immunotherapy and offer new therapeutic insights.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
Jessica N. Everett, Gabriela Burgos, Jennifer Chun, Ariele Baptiste, Lauren G. Khanna, Paul E. Oberstein, Diane M. Simeone
Summary: The study found that surveillance for PDAC is underutilized in high-risk families, with lack of awareness and interest being the primary reasons for nonparticipation. At-risk relatives with familial pancreatic cancer who also carried relevant pathogenic germline variants were more likely to undergo surveillance.
Article
Multidisciplinary Sciences
Yong Xia, Yan Liu, Chao Yang, Diane M. Simeone, Tung-Tien Sun, David J. DeGraff, Moon-shong Tang, Yingkai Zhang, Xue-Ru Wu
Summary: The human chromosome locus 9p21.3 encodes three CDK inhibitors, among which p15INK4B exhibits stronger inhibitory effects on cell cycle and glycolysis compared to p16INK4A, highlighting its significant role as a tumor suppressor in cancer development.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Gastroenterology & Hepatology
Tamas A. Gonda, Jessica N. Everett, Michael Wallace, Diane M. Simeone
Review
Cell Biology
Gregory L. Beatty, Gregor Werba, Costas A. Lyssiotis, Diane M. Simeone
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related mortality in the United States, with a low survival rate of 10% over 5 years. The disease demonstrates remarkable adaptability and resistance to therapeutic intervention, contributing to its poor prognosis. Recent advances in understanding the biological underpinnings of PDAC have revealed potential vulnerabilities that can be targeted for treatment.
GENES & DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Annie Wang, Jessica N. Everett, Jennifer Chun, Cindy Cen, Diane M. Simeone, Freya Schnabel
Summary: This study found that breast cancer patients with a family history of pancreatic cancer were more likely to undergo genetic testing, but still a significant proportion did not receive testing or were incompletely tested, suggesting a potential underestimation of pancreatic cancer risk.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Brian M. Larsen, Madhavi Kannan, Lee F. Langer, Benjamin D. Leibowitz, Aicha Bentaieb, Andrea Cancino, Igor Dolgalev, Bridgette E. Drummond, Jonathan R. Dry, Chi-Sing Ho, Gaurav Khullar, Benjamin A. Krantz, Brandon Mapes, Kelly E. McKinnon, Jessica Metti, Jason F. Perera, Tim A. Rand, Veronica Sanchez-Freire, Jenna M. Shaxted, Michelle M. Stein, Michael A. Streit, Yi-Hung Carol Tan, Yilin Zhang, Ende Zhao, Jagadish Venkataraman, Martin C. Stumpe, Jeffrey A. Borgia, Ashiq Masood, Daniel V. T. Catenacci, Jeremy Mathews, Demirkan B. Gursel, Jian-Jun Wei, Theodore H. Welling, Diane M. Simeone, Kevin P. White, Aly A. Khan, Catherine Igartua, Ameen A. Salahudeen
Summary: A robust pan-cancer tumor organoid platform with chemically defined media has been established and neural-network-based high-throughput method has been demonstrated to predict patient-specific heterogeneity in drug responses. These resources are expected to accelerate the broad implementation of organoid models in precision medicine research and personalized therapeutic profiling programs.
Article
Gastroenterology & Hepatology
Tamas A. Gonda, James Farrell, Michael Wallace, Lauren Khanna, Eileen Janec, Richard Kwon, Michael Saunders, Uzma D. Siddiqui, Randall Brand, Diane M. Simeone
Summary: The adoption of a standardized EUS reporting template will improve consistency in clinical decision-making for individuals at risk of pancreatic cancer and provide complete and accurate reporting of pancreatic abnormalities. Standardization will also facilitate research and clinical trial design, allowing for comparison of results across different centers.
GASTROINTESTINAL ENDOSCOPY
(2022)
Review
Gastroenterology & Hepatology
Laura D. Wood, Marcia Irene Canto, Elizabeth M. Jaffee, Diane M. Simeone
Summary: This review discusses the pathogenesis, early detection methods, and treatment considerations of pancreatic ductal adenocarcinoma (PDAC). Recent advances in understanding PDAC have led to significant improvements in detection and treatment, but coordinated efforts are needed to maximize clinical impact for patients and overall survival.
Review
Radiology, Nuclear Medicine & Medical Imaging
Chenchan Huang, Diane M. Simeone, Lyndon Luk, Elizabeth M. Hecht, Gaurav Khatri, Avinash Kambadakone, Hersh Chandarana, Justin M. Ream, Jessica N. Everett, Alexander Guimaraes, Joy Liau, Anil K. Dasyam, Carla Harmath, Alec J. Megibow
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor survival rates. High-risk individuals are recommended to have regular screening with MRI and/or endoscopic ultrasound. The Pancreatic Cancer Early Detection (PRECEDE) Consortium aims to increase survival of PDAC by facilitating earlier diagnosis through standardized MRI screening and reporting.
AMERICAN JOURNAL OF ROENTGENOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Minh Huynh, G. Aaron Hobbs, Antje Schaefer, Mariaelena Pierobon, Leiah M. Carey, J. Nathaniel Diehl, Jonathan M. DeLiberty, Ryan D. Thurman, Adelaide R. Cooke, Craig M. Goodwin, Joshua H. Cook, Lin Lin, Andrew M. Waters, Naim U. Rashid, Emanuel F. Petricoin, Sharon L. Campbell, Kevin M. Haigis, Diane M. Simeone, Costas A. Lyssiotis, Adrienne D. Cox, Channing J. Der
Summary: Missense mutations at the three hotspots in RAS-Gly(12), Gly(13), and Gln(61) show differential distribution among the three RAS isoforms. KRAS(Q61) mutants exhibit various changes in morphology, growth transformation, effector signaling, and metabolism. Differences in biochemical, structural, and biological properties may explain the frequency variations. Targeting KRAS(Q61) mutant-specific signaling and cellular output may be a potential therapeutic strategy.
Article
Oncology
Jessica N. Everett, Shenin A. Dettwyler, Xiaohong Jing, Cody Stender, Madeleine Schmitter, Ariele Baptiste, Jennifer Chun, Emily A. Kawaler, Lauren G. Khanna, Seth A. Gross, Tamas A. Gonda, Nina Beri, Paul E. Oberstein, Diane M. Simeone
Summary: Integrating genetics into a multidisciplinary setting improves compliance with genetic testing for pancreatic ductal adenocarcinoma (PDAC) patients, reduces logistical barriers, and clarifies cancer risks for relatives.
Article
Oncology
Jiheng Xu, Rui Yang, Jingxia Li, Lidong Wang, Mitchell Cohen, Diane M. Simeone, Max Costa, Xue-Ru Wu
Summary: The stem-cell-like behavior of cancer cells in bladder cancer plays a crucial role and its molecular basis remains incompletely defined. This study demonstrates that SNHG1 induces the formation of stem-cell-like spheres and invasion of bladder cancer cells by upregulating Rho GTPase, Rac1. SNHG1 binds to DNMT3A and represses the transcription of miR-129-2-5p, resulting in increased Rac1 protein levels. High expression of Rac1 is associated with poor prognosis in bladder cancer patients.
Article
Gastroenterology & Hepatology
Sharon Pan, Lisa A. Lai, Diane M. M. Simeone, David W. W. Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A. Brentnall
Summary: Proteomic and functional analysis of extracellular vesicles (EVs) released from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) identified over 1400 nonredundant proteins involved in vesicle-mediated transport and exocytosis. Protein networks relevant to pancreatic tumorigenesis, such as epithelial-mesenchymal transition, complement, and coagulation components, were significantly enriched in EVs from cancer cells or CAFs, suggesting a potential role of EVs in mediating signals related to tumorigenesis and microenvironment interactions.