Article
Multidisciplinary Sciences
Jingying Zhou, Huanyu Wang, Ting Shu, Jing Wang, Weiqin Yang, Jingqing Li, Lipeng Ding, Man Liu, Hanyong Sun, John Wong, Paul Bo-san Lai, Shun-Wa Tsang, Simon E. Ward, King-Lau Chow, Joseph Jao-yiu Sung, Alfred Sze-Lok Cheng
Summary: Massive expansion of immature and suppressive myeloid cells is a common feature of malignant solid tumors. Over-expression of cyclin-dependent kinase 20 in hepatocellular carcinoma correlates with reduced patient survival and low immunotherapy responsiveness. Here, we showed that CCRK is upregulated in myeloid cells in tumor-bearing mice and in patients with HCC. Inactivation of Ccrk in myeloid cells confers a mature phenotype and increases IL-12 production, leading to reduced tumor growth and prolonged survival. Mechanistically, CCRK activates STAT3/E4BP4 signaling to induce immunosuppression. Our findings provide insights into MDSC-mediated immunosuppression and offer a potential kinase-target for cancer immunotherapy.
Article
Biochemistry & Molecular Biology
Kunhua Hu, Yufeng Ding, Hongwen Zhu, Xiaoqian Jing, Weiling He, Hua Yu, Xiongjun Wang
Summary: Tumor cells surviving hypoxic stress acquire the ability to drive cancer progression. Glutamate dehydrogenase 1 (GDH1) plays a critical role in regulating colorectal cancer (CRC) cell survival under hypoxia. GDH1 deficiency inhibits CRC occurrence and impairs hypoxia-inducible factor 1-alpha (HIF-1a) stability, promoting CRC progression through the modulation of GDH1 acetylation at K503 and K527.
Article
Oncology
Xintian Chen, Zhongwei Li, Hongmei Yong, Wenwen Wang, Diandian Wang, Sufang Chu, Minle Li, Pingfu Hou, Junnian Zheng, Jin Bai
Summary: Trim21 is downregulated in primary RCC tissues, leading to poor prognosis. It inhibits RCC cells glycolysis by degrading HIF-1 alpha, thereby reducing their proliferation and metastasis capabilities. Trim21 may serve as a promising predictive biomarker for RCC patient prognosis.
Article
Oncology
Giusi La Camera, Luca Gelsomino, Rocco Malivindi, Ines Barone, Salvatore Panza, Daniela De Rose, Francesca Giordano, Vittoria D'Esposito, Pietro Formisano, Daniela Bonofiglio, Sebastiano Ando, Cinzia Giordano, Stefania Catalano
Summary: The study demonstrates that adipocyte-derived EVs can enhance breast cancer cell malignancy through the induction of HIF-1 alpha activity, with EV release in obese settings playing a potentially key role in breast cancer progression.
Article
Biochemistry & Molecular Biology
Moon Jong Kim, Christopher Cervantes, Youn-Sang Jung, Xiaoshan Zhang, Jie Zhang, Sung Ho Lee, Sohee Jun, Larisa Litovchick, Wenqi Wang, Junjie Chen, Bingliang Fang, Jae-Il Park
Summary: PAF drives cell quiescence exit to promote lung tumorigenesis by remodeling the DREAM complex. Its depletion induces cell quiescence in lung adenocarcinoma cells and inhibits tumor growth, suggesting the PAF-DREAM axis as a potential therapeutic target in lung cancer.
Article
Oncology
Emma Phillips, Jorg Balss, Frederic Bethke, Stefan Pusch, Stefan Christen, Thomas Hielscher, Martina Schnoelzer, Michael N. C. Fletcher, Antje Habel, Claudia Tessmer, Lisa-Marie Brenner, Mona Goettmann, David Capper, Christel Herold-Mende, Andreas von Deimling, Sarah-Maria Fendt, Violaine Goidts
Summary: The study reveals the crucial role of PFKFB4 in glioblastoma growth, showing its involvement in regulating the degradation of HIF-1α. Furthermore, the overexpression of PFKFB4 in other cancer entities suggests its potential as a target for cancer therapy.
Article
Biochemistry & Molecular Biology
Leonard A. Daly, Philip J. Brownridge, Michael Batie, Sonia Rocha, Violaine See, Claire E. Eyers
Summary: Cellular adaptation to low-oxygen environments is partially mediated by hypoxia-inducible factors (HIFs), whose stability and activity are regulated by post-translational modifications (PTMs) and protein-protein interactions. Hypoxia alters the complexity and composition of HIF alpha protein interaction networks, particularly for HIF-2 alpha, with the networks enriched for mitochondrial proteins. Additionally, both HIF alpha isoforms undergo heavy covalent modifications, with a majority of newly identified PTMs exhibiting oxygen dependency.
Article
Cell Biology
Jinghui Lei, Xiaoyu Jiang, Daoyuan Huang, Ying Jing, Shanshan Yang, Lingling Geng, Yupeng Yan, Fangshuo Zheng, Fang Cheng, Weiqi Zhang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Si Wang, Jing Qu
Summary: Using CRISPR/Cas9 gene editing, researchers investigated the response mechanism of human vascular cells to HIF-1α under hypoxic conditions. They found that HIF-1α plays an important role in promoting ischemic vascular regeneration and that MSCs are particularly susceptible to HIF-1α deficiency. Transcriptional inactivation of ANKZF1, an effector of HIF-1α, was found to impair pro-angiogenic processes.
Article
Gastroenterology & Hepatology
Hulin Chang, Jibin Li, Ying Luo, Bing Wu, Chong Yuan, Xilin Geng
Summary: TFB2M plays a critical role in enhancing the reprogramming of glucose metabolism in HCC cells, mainly through upregulation of glycolytic genes and downregulation of PGC-1 alpha, thus promoting cancer progression and metastasis through HIF-1 alpha-regulated mechanisms.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Oncology
Qiuli Liu, Jian Pang, Lin-ang Wang, Zhuowei Huang, Jing Xu, Xingxia Yang, Qiubo Xie, Yiqiang Huang, Tang Tang, Dali Tong, Gaolei Liu, Luofu Wang, Dianzheng Zhang, Qiang Ma, Hualiang Xiao, Weihua Lan, Jun Qin, Jun Jiang
Summary: The study demonstrates that PHF8 is essential for the development of NEPC by transcriptionally upregulating the FOXA2 gene, which regulates the expression of genes involved in NEPC development. Both PHF8 and FOXA2 could potentially serve as biomarkers for NEPC and targeting them may be a therapeutic strategy for NEPC treatment.
JOURNAL OF PATHOLOGY
(2021)
Article
Oncology
Bin Zhao, Xiulong Niu, Suhui Huang, Jing Yang, Yiyi Wei, Xiujuan Wang, Junhong Wang, Yue Wang, Xiaoqin Guo
Summary: Inflammation and hypoxia are involved in the progression of epithelial ovarian cancer, and a possible positive correlation among TLR4, NF-κB, and HIF-1α proteins has been found. The study suggests the formation of a TLR4/NF-κB/HIF-1α loop in EOC, which enhances susceptibility and responsiveness to inflammation and hypoxia, promoting the initiation and progression of EOC. This novel mechanism may serve as a potential therapeutic target for EOC treatment.
ANALYTICAL CELLULAR PATHOLOGY
(2022)
Article
Oncology
Hye Jin Yun, Min Li, Dong Guo, So Mi Jeon, Su Hwan Park, Je Sun Lim, Su Bin Lee, Rui Liu, Linyong Du, Seok-Ho Kim, Tae Hwan Shin, Seong-il Eyun, Yun-Yong Park, Zhimin Lu, Jong-Ho Lee
Summary: This study reveals that enhanced glucose-derived de novo serine biosynthesis is a critical metabolic feature of GBM cells under metabolic stress, and highlights the potential to target SSP for treating human GBM.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Neurosciences
Qi Wang, Chi Zhang, Junle Zhu, Lei Zhang, Huairui Chen, Jun Qian, Chun Luo
Summary: RLIP76 is a hypoxia-inducible protein that promotes glycolysis in glioma cells. It activates glycolytic proteins GLUT1 and LDHA by binding to HIF-1a and regulating its stability, accelerating glycolysis in hypoxia. Furthermore, RLIP76 plays a necessary role in enhancing glycolysis in glioma development.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hongjun Song, Zhongling Qiu, Yang Wang, Chuang Xi, Guoqiang Zhang, Zhenkui Sun, Quanyong Luo, Chentian Shen
Summary: This study revealed a novel regulatory mechanism of glucose/iodine metabolic reprogramming in papillary thyroid cancer (PTC). Under hypoxic conditions, YAP activation accelerated glycolysis and reduced the expression of NIS. In addition, the HIF-1 alpha/YAP signaling indirectly reduced NIS expression. These findings have important implications for understanding the development of aggressive PTC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Immunology
Charles Thomas, Damien Leleu, David Masson
Summary: HIF-1α plays a dual role in atherosclerosis, with both detrimental and beneficial effects. Its impact depends on the cell type expressing HIF-1α, and it can be stabilized by oxLDLs and oxysterols, leading to various responses including inflammation, angiogenesis, and metabolic reprogramming. Additionally, HIF-1α promotes the accumulation of cholesterol and triglycerides in macrophages.
FRONTIERS IN IMMUNOLOGY
(2022)
