Review
Gastroenterology & Hepatology
Samantha B. Kemp, Marina Pasca di Magliano, Howard C. Crawford
Summary: Pancreatic ductal adenocarcinoma (PDA) is a nearly universally lethal malignancy characterized by extensive infiltration of immunosuppressive myeloid cells, inhibiting normal immune functions and promoting carcinogenesis. Current immune checkpoint therapy has not been effective in PDA, highlighting the importance of understanding the mechanisms underlying immune suppression in this type of cancer.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Ryota Takahashi, Marina Macchini, Masaki Sunagawa, Zhengyu Jiang, Takayuki Tanaka, Giovanni Valenti, Bernhard W. Renz, Ruth A. White, Yoku Hayakawa, C. Benedikt Westphalen, Yagnesh Tailor, Alina C. Iuga, Tamas A. Gonda, Jeanine Genkinger, Kenneth P. Olive, Timothy C. Wang
Summary: The study demonstrates that IL-1 beta promotes tumorigenesis by inducing an expansion of immune-suppressive B cells. These findings highlight the growing significance of B suppressor cells in pancreatic tumorigenesis.
Article
Oncology
Dayong Han, Na Zhang, Shu Zhao, Huailei Liu, Xiaoxiong Wang, Mingchun Yang, Shengtao Wang, Yue Li, Zhanwen Liu, Lei Teng
Summary: This study reveals that in glioblastoma multiforme, AKIP1 promotes cell proliferation, invasion, and chemoradiation resistance by regulating pathways mediated by CXCL1 and CXCL8, potentially providing new therapeutic targets for future treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Puhua Zhang, Chaolun Yu, Jianwen Yu, Zhijian Li, Hui-yao Lan, Qin Zhou
Summary: The lncRNA Arid2-IR plays a critical role in kidney diseases by regulating NF-kappa B signaling via a NLRC5-dependent mechanism, which can be inhibited by Filamin A in the cytoplasm. Targeting Arid2-IR may be a novel therapeutic strategy for inflammatory diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Oncology
Weijun Wu, Jinghuan Wang, Chenxi Xiao, Zhenghua Su, Haibi Su, Wen Zhong, Jianchun Mao, Xinhua Liu, Yi Zhun Zhu
Summary: This study confirmed that cytoplasmic protein TRAF2 can be methylated by SMYD2 and contribute to the continuous activation of NF-kappa B signaling pathway. Knocking down SMYD2 showed varying degrees of mitigation in acute and chronic inflammation mouse models. Moreover, lysine-specific demethylase LSD1 was found to resist the methylation of TRAF2 induced by SMYD2.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Hua Huang, Ruining Pan, Yue Zhao, Huan Li, Huiyu Zhu, Sijia Wang, Aamir Ali Khan, Juan Wang, Xinhui Liu
Summary: This study reveals the crucial roles of L3MBTL2 and CGA in tumor development. L3MBTL2 represses CGA through an H2AK119ub1-dependent mechanism, and the individual tumor suppressor role of CGA in PDAC is partly dependent on its own glycosylation.
Article
Multidisciplinary Sciences
Dongwen Que, Feimei Kuang, Rui Kang, Daolin Tang, Jiao Liu
Summary: Alkaliptosis is a newly discovered pH-dependent cell death used for tumor therapy. ACSS2, an acetate-activating enzyme, is identified as a positive regulator of alkaliptosis in human PDAC cells. ACSS2 expression is upregulated in response to the alkaliptosis activator JTC801, and knockdown of ACSS2 inhibits JTC801-induced cell death and alters cellular pH. These findings provide new insights into the metabolic basis of alkaliptosis and potential strategies for PDAC treatment.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Masataka Hayashi, Naoki Ikenaga, Kohei Nakata, Haizhen Luo, PingShan Zhong, Satomi Date, Koki Oyama, Nobuhiro Higashijima, Akihiro Kubo, Chika Iwamoto, Nobuhiro Torata, Toshiya Abe, Yutaka Yamada, Kenoki Ohuchida, Yoshinao Oda, Masafumi Nakamura
Summary: Intratumor bacteria, such as Fusobacterium nucleatum, can influence the tumor immune microenvironment and affect the prognosis of pancreatic cancer. In this study, F. nucleatum was detected in 15.5% of pancreatic cancer patients and was associated with larger tumor size. F. nucleatum promoted cancer progression by inducing CXCL1 secretion from cancer cells and suppressing tumor-infiltrating CD8(+) T cells. Blocking the CXCL1-CXCR2 axis may be a potential therapeutic strategy for patients with F. nucleatum-positive pancreatic cancer.
Article
Pharmacology & Pharmacy
Yanhong Pan, Yanping You, Li Sun, Qibang Sui, Liu Liu, Haoliang Yuan, Caiping Chen, Jun Liu, Xiaoan Wen, Liang Dai, Hongbin Sun
Summary: STING and its downstream target genes were up-regulated in lesional skin samples from psoriasis patients. Topical application of H-151 inhibited skin lesions in a psoriatic mouse model, as well as the secretion of pro-inflammatory cytokines and activation of immune cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Qian Zhang, Kun Yu, Yazhen Cao, Yanli Luo, Yan Liu, Caiyan Zhao
Summary: The study revealed that miR-125b expression is up-regulated in NAFLD patients, along with increased levels of inflammatory-related genes in the liver. MiR-125b promotes NF-kappa B-mediated inflammatory responses by directly targeting TNFAIP3, suggesting it as a potential target for treating NAFLD.
Article
Oncology
Yan Du, Zechang Xin, Tongtai Liu, Peng Xu, Feiyu Mao, Jie Yao
Summary: The study revealed significant downregulation of CA12 in PAAD tissue samples, with lower CA12 expression associated with poorer overall survival. CA12 overexpression inhibited the proliferation of PAAD cell lines, leading to apoptotic death and G0/G1 phase cell cycle arrest. Additionally, it was found that CA12 may exert its tumor suppressive roles through modulation of the NF-kappa B signaling pathway.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Dong Guo, Yingying Tong, Xiaoming Jiang, Ying Meng, Hongfei Jiang, Linyong Du, Qingang Wu, Shan Li, Shudi Luo, Min Li, Liwei Xiao, Haiyan He, Xuxiao He, Qiujing Yu, Jing Fang, Zhimin Lu
Summary: High glucose promotes PD-L1 expression in tumor cells, leading to tumor immune evasion. Inhibition of HK2 and PD-1 can eliminate tumor immune evasion and enhance the anti-tumor effect of immune checkpoint blockade.
Article
Immunology
Huimin Hu, Ming Fu, Chuntian Li, Binman Zhang, Yuncheng Li, Qinxue Hu, Mudan Zhang
Summary: HSV-2 inhibits the activation of NF-kappa B through the immediate early protein ICP22, suggesting a novel mechanism by which HSV-2 evades the host antiviral responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Shanshan Teng, Jie Hao, Hui Bi, Congcong Li, Yongfeng Zhang, Yaqin Zhang, Weiwei Han, Di Wang
Summary: The study found that crocin has protective effects against UC and CRC by suppressing inflammation mediated by NF-kappa B. Crocin reduced disease activity index scores, improved colonic epithelium symptoms, and inhibited tumor growth. Crocin also decreased concentrations of interleukins and tumor necrosis factor-alpha, showing its anti-inflammatory effects.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Wenting Du, Marina Pasca di Magliano, Yaqing Zhang
Summary: The stroma-rich, immunosuppressive microenvironment in PDA is characterized by interactions between tumor cells and other cellular components, leading to immune evasion and contributing to cancer cell phenotypes. Therapeutic approaches targeting the stroma and re-programming the tumor microenvironment may improve clinical outcomes for pancreatic cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Oncology
Brian A. Van Tine, Costas A. Lyssiotis
Summary: Mass action drives the serum homeostasis of metabolites. Recent developments in biofluid metabolomics suggest the potential to harness these changes using small volumes of blood to diagnose, monitor, and risk stratify patients with cancer. This current study may represent a complementary technology to circulating tumor DNA detection.
CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Nneka E. Mbah, Costas A. Lyssiotis
Summary: In this article, the intrinsic and extrinsic factors that promote the sensitivity of cancer cells to ferroptosis were reviewed, including the components of the tumor microenvironment. Also, the potential therapeutic options for cancer therapy utilizing ferroptotic agents were described.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Roshan Kumar, Aaron P. Landry, Arkajit Guha, Victor Vitvitsky, Ho Joon Lee, Keisuke Seike, Pavan Reddy, Costas A. Lyssiotis, Ruma Banerjee
Summary: The dual roles of H2S as a respiratory substrate and toxin raise questions about how it is cleared when the electron transport chain is inhibited. This study discovered a newly established redox cycle between SQOR and complex II at high H2S concentrations, which plays a significant role in prioritizing H2S oxidation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Zeribe Chike Nwosu, Mun Gu Song, Marina Pasca di Magliano, Costas A. A. Lyssiotis, Sung Eun Kim
Summary: Cancer cells depend on specific extracellular nutrients for their metabolism and growth. SLC transporters play a crucial role in acquiring these nutrients and transferring intracellular nutrients. Understanding the function of SLC transporters in cancer could provide therapeutic targets for effective treatment.
Article
Chemistry, Multidisciplinary
Hyeoncheol Kim, Luke B. Villareal, Zhaoli Liu, Mohammad Haneef, Daniel M. Falcon, David R. Martin, Ho-Joon Lee, Michael K. Dame, Durga Attili, Ying Chen, James Varani, Jason R. Spence, Olga Kovbasnjuk, Justin A. Colacino, Costas A. Lyssiotis, Henry C. Lin, Yatrik M. Shah, Xiang Xue
Summary: This study reveals that transferrin receptor (TFRC) is induced by β-catenin activation driven by APC gene loss in colorectal cancer, and TFRC-mediated intratumoral iron accumulation enhances β-catenin signaling through tankyrase activation. Disruption of TFRC reduces colonic iron levels and iron-dependent tankyrase activity, leading to stabilization of AXIN2 and repression of the β-catenin/c-Myc/E2F Transcription Factor 1/DNA polymerase delta1 (POLD1) axis, causing increased DNA replication stress, DNA damage response, apoptosis, and reduced colon tumor growth. Iron chelation combined with DNA damaging agents further increases DNA damage response and reduces colon tumor cell growth. This discovery may offer new strategies for colorectal cancer therapy.
Article
Multidisciplinary Sciences
Mack B. Reynolds, Hanna S. Hong, Britton C. Michmerhuizen, Anna-Lisa E. Lawrence, Li Zhang, Jason S. Knight, Costas A. Lyssiotis, Basel H. Abuaita, Mary X. O'Riordan
Summary: Macrophage metabolic plasticity allows the redirection of electron transport for inflammation and host defense. Inflammatory activation leads to disassembly of Complex II and loss of succinate dehydrogenase subunit B through sequestration and selective mitophagy. The regulatory role of cardiolipin in coordinating Complex II function and inflammatory metabolic remodeling is demonstrated.
Article
Immunology
Hanna S. Hong, Nneka E. Mbah, Mengrou Shan, Kristen Loesel, Lin Lin, Peter Sajjakulnukit, Luis O. Correa, Anthony Andren, Jason Lin, Atsushi Hayashi, Brian Magnuson, Judy Chen, Zhaoheng Li, Yuying Xie, Li Zhang, Daniel R. Goldstein, Shannon A. Carty, Yu Leo Lei, Anthony W. Opipari, Rafael J. Arguello, Ilona Kryczek, Nobuhiko Kamada, Weiping Zou, Luigi Franchi, Costas A. Lyssiotis
Summary: This study demonstrates the importance of metabolism in regulating the fate of T(H)17 cells and highlights the potential for targeting mitochondrial oxidative phosphorylation (OXPHOS) in T(H)17-driven diseases.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lingxin Zhu, Yi Tang, Xiao-Yan Li, Samuel A. Kerk, Costas A. Lyssiotis, Wenqing Feng, Xiaoyue Sun, Geoffrey E. Hespe, Zijun Wang, Marc P. Stemmler, Simone Brabletz, Thomas Brabletz, Evan T. Keller, Jun Ma, Jung-Sun Cho, Jingwen Yang, Stephen J. Weiss
Summary: Osteoclasts undergo transcriptional and metabolic changes during differentiation to acquire the cellular machinery for bone resorption. Zeb1, a zinc-finger transcriptional repressor, is found to play a role in osteoclast energy metabolism. By repressing a crucial enzyme involved in ATP buffering and mitochondrial respiration, Zeb1 controls the activity of osteoclasts and influences bone remodeling. This study reveals a novel Zeb1/MtCK1 axis that regulates bone resorption through metabolic control.
Article
Biochemistry & Molecular Biology
Brandon Chen, Nupur K. Das, Indrani Talukder, Rashi Singhal, Cristina Castillo, Anthony Andren, Joseph D. Mancias, Costas A. Lyssiotis, Yatrik M. Shah
Summary: PINK1 plays a positive role in colorectal cancer by promoting tumor survival and growth through regulating mitophagy and ferritinophagy pathways, which regulate intracellular iron availability and stability.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Cell Biology
Lingxin Zhu, Yi Tang, Xiao-Yan Li, Samuel A. Kerk, Costas A. Lyssiotis, Xiaoyue Sun, Zijun Wang, Jung-Sun Cho, Jun Ma, Stephen J. Weiss
Summary: The interaction between metalloproteins Mmp9 and Mmp14 and carbohydrate-binding protein galectin-3 plays a critical role in osteoclast-mediated bone resorption. The ability of Mmp9 and Mmp14 to degrade galectin-3 on the cell surface depends on its binding protein Lrp-1. These findings reveal a previously unrecognized galectin-3/Lrp1 axis that regulates both the transcriptional programs and intracellular signaling cascades essential for osteoclast function.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Zeribe C. Nwosu, Matthew H. Ward, Peter Sajjakulnukit, Pawan Poudel, Chanthirika Ragulan, Steven Kasperek, Megan Radyk, Damien Sutton, Rosa E. Menjivar, Anthony Andren, Juan J. Apiz-Saab, Zachary Tolstyka, Kristee Brown, Ho-Joon Lee, Lindsey N. Dzierozynski, Xi He, P. S. Hari, Julia Ugras, Gift Nyamundanda, Li Zhang, Christopher J. Halbrook, Eileen S. Carpenter, Jiaqi Shi, Leah P. Shriver, Gary J. Patti, Alexander Muir, Marina Pasca di Magliano, Anguraj Sadanandam, Costas A. Lyssiotis
Summary: Pancreatic ductal adenocarcinoma (PDA) is a highly resistant and lethal disease, driven by a complex tumor microenvironment, low vascularity, and metabolic aberrations. This study reveals that uridine is utilized as a fuel by PDA cells under glucose-deprived conditions. Uridine is metabolized by uridine phosphorylase 1 (UPP1) to support central carbon metabolism and promote survival and proliferation in nutrient-restricted PDA cells. UPP1 expression is regulated by KRAS-MAPK signaling and is correlated with poor survival in PDA patients. Moreover, UPP1 deletion impairs uridine utilization and inhibits tumor growth in mouse models. These findings suggest a novel metabolic axis for PDA therapy.
Article
Oncology
Eileen S. Carpenter, Ahmed M. Elhossiny, Padma Kadiyala, Jay Li, Jake McGue, Brian D. Griffith, Yaqing Zhang, Jacob Edwards, Sarah Nelson, Fatima Lima, Katelyn L. Donahue, Wenting Du, Allison C. Bischoff, Danyah Alomari, Hannah R. Watkoske, Michael Mattea, Stephanie The, Carlos E. Espinoza, Meredith Barrett, Christopher J. Sonnenday, Nicholas Olden, Chin-Tung Chen, Nicole Peterson, Valerie Gunchick, Vaibhav Sahai, Arvind Rao, Filip Bednar, Jiaqi Shi, Timothy L. Frankel, Marina Pasca di Magliano
Summary: We characterized the unique microenvironment of the adult human pancreas and discovered the high prevalence of PanIN lesions compared to pancreatic cancer. Fibroblasts and macrophages in pancreatic cancer and peritumoral tissue showed distinct transcriptomic signatures. PanIN epithelial cells in healthy pancreas exhibited remarkable similarity to cancer cells transcriptionally, suggesting early initiation of neoplastic pathways in tumorigenesis.
Article
Biology
Juan J. Apiz Saab, Lindsey N. Dzierozynski, Patrick B. Jonker, Roya AminiTabrizi, Hardik Shah, Rosa Elena Menjivar, Andrew J. Scott, Zeribe C. Nwosu, Zhou Zhu, Riona N. Chen, Moses Oh, Colin Sheehan, Daniel R. Wahl, Marina Pasca di Magliano, Costas A. Lyssiotis, Kay F. Macleod, Christopher R. Weber, Alexander Muir
Summary: Nutrient stress in the tumor microenvironment affects cancer cell metabolism and behavior. By studying the tumor interstitial fluid medium, it has been found that PDAC cells cultured in this medium resemble their in vivo state more closely, and arginine biosynthesis is crucial for maintaining arginine levels in PDAC cells.
Meeting Abstract
Oncology
Yaqing Zhang, Kristee L. Brown, Wei Yan, Zeribe C. Nwosu, Eileen K. Carpenter, Katelyn L. Donahue, Ashley Velez-Delgado, Sion Yang, Marina Pasca di Magliano
CANCER IMMUNOLOGY RESEARCH
(2022)