Article
Biochemistry & Molecular Biology
Jiunn-Chang Lin, Pei-Ming Yang, Tsang-Pai Liu
Summary: The study identified lncRNA ZFAS1 as a potential biomarker for sorafenib therapy resistance in HCC, and showed that sorafenib induces ER stress and the unfolded protein response pathways through the PERK/ATF4/ZFAS1 signaling axis. This finding suggests a new direction for the treatment and prognosis of HCC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chao-Yuan Huang, Li-Ju Chen, Grace Chen, Tzu- Chao, Cheng-Yi Wang
Summary: This study reveals that sorafenib induces ferroptosis in hepatocellular carcinoma (HCC) by enhancing SHP-1 activity, downregulating MCL1 expression, and reducing the association between MCL1 and BECN1. Additionally, sorafenib treatment increases the binding between BECN1 and SLC7A11, leading to inhibition of system Xc(-). Silencing BECN1 restores cystine intake and protects cells from ferroptosis. MCL1 overexpression decouples BECN1 from SLC7A11 and rescues cell viability by attenuating lipid peroxidation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Ting Liu, Xiao-Li Xie, Xue Zhou, Sheng-Xiong Chen, Yi-Jun Wang, Lin-Ping Shi, Shu-Jia Chen, Yong-Juan Wang, Shu-Ling Wang, Jiu-Na Zhang, Shi-Ying Dou, Xiao-Yu Jiang, Ruo-Lin Cui, Hui-Qing Jiang
Summary: YB-1, overexpressed in HCC tissues, enhances sorafenib resistance through the PI3K/Akt pathway. Knockdown of YB-1 can improve the efficacy of sorafenib in vivo. The interaction between YB-1 and key proteins of the PI3K/Akt pathway contributes to sorafenib resistance in HCC.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Cell & Tissue Engineering
Jie Zhou, Junying Yang, Yuan Dong, Yaru Shi, Endong Zhu, Hairui Yuan, Xiaoxia Li, Baoli Wang
Summary: Our study has for the first time established the direct role of OSMR in regulating osteogenic differentiation of marrow stromal progenitor cells through ERK-mediated autophagy signaling. OSMR thus contributes to bone homeostasis through dual regulation of osteoblasts and osteoclasts. It also suggests that OSMR may be a potential target for the treatment of metabolic disorders such as osteoporosis.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Gastroenterology & Hepatology
Wen-Zhi Qu, Luan Wang, Juan-Juan Chen, Yang Wang
Summary: This study aims to detect the expression of RKIP, P-ERK, and P-MEK proteins in GIST and analyze their relationship with clinicopathological characteristics and prognosis. A new prognosis evaluation model using RKIP and P-ERK is established and its efficacy is evaluated.
WORLD JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Yan Huang, Chenxu Zhao, Yaoquan Liu, Yezi Kong, Panpan Tan, Siqi Liu, Fangyuan Zeng, Yang Yuan, Xinwei Li, Guowen Liu, Baoyu Zhao, Jianguo Wang
Summary: The study shows that NEFA can activate hepatocyte autophagy through the PERK pathway, contributing to lipid metabolism. These findings enhance our understanding of energy redistribution and utilization during the perinatal period of dairy cows.
Review
Toxicology
Yujia Xie, Jixuan Ma, Meng Yang, Lieyang Fan, Weihong Chen
Summary: Silicosis is a scarring lung disease caused by inhaling fine particles of crystalline silica in the workplace. The underlying molecular mechanisms of silicosis are not fully understood, but recent studies have highlighted the role of the activated ERK signaling pathway in regulating oxidative stress, inflammatory response, fibroblast activation, and other processes involved in the formation and development of silicosis.
TOXICOLOGY RESEARCH
(2021)
Article
Oncology
Ye Yang, Ming Jin, Yi Dai, Wenqi Shan, Shuai Chen, Rong Cai, Haojun Yang, Liming Tang, Lei Li
Summary: The study uncovered the mechanisms by which mortalin contributes to angiogenesis and sorafenib resistance in HCC cells, and identified caffeic acid as a novel chemical inhibitor that targets mortalin's function, potentially offering a new treatment approach for HCC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Na Zhuang, Zhiyun Gu, Juan Feng, Zixuan Chai, Juanjuan Shan, Cheng Qian
Summary: This study identified BEX1 as a key mediator of sorafenib resistance in hepatocellular carcinoma (HCC). It was found that reduced BEX1 expression was correlated with poor clinical prognosis in HCC patients. BEX1 increases the sensitivity of HCC cells to sorafenib through induction of apoptosis and negative regulation of Akt phosphorylation.
CELLULAR SIGNALLING
(2023)
Article
Plant Sciences
Chen Yang, Tao Lu, Ming Liu, Xiaoqing Yuan, Desheng Li, Jiayu Zhang, Ling Zhou, Maolei Xu
Summary: In this study, it was found that tiliroside, a natural flavonoid glycoside isolated from oriental paperbush flower, could enhance the sensitivity of hepatocellular carcinoma (HCC) cells to sorafenib by inhibiting the enzymatic activity of TBK1 and degrading Nrf2 to induce ferroptosis. These findings imply that tiliroside may be a potential small molecule drug that can function as a sensitizer of sorafenib in HCC treatment by targeting TBK1.
Article
Multidisciplinary Sciences
Atsushi Yukimoto, Takao Watanabe, Kotaro Sunago, Yoshiko Nakamura, Takaaki Tanaka, Yohei Koizumi, Osamu Yoshida, Yoshio Tokumoto, Masashi Hirooka, Masanori Abe, Yoichi Hiasa
Summary: The study uncovers the close relationship between PERK and RMRP in HCC, with downregulation of RMRP inducing apoptotic cell death. This suggests RMRP could be a potential new therapeutic target for regulating HCC in patients with chronic liver diseases associated with ER stress.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Xiang-Peng Tan, Ben-Han Xiong, Yuan-Xu Zhang, Shen-Li Wang, Qian Zuo, Jing Li
Summary: This study discovered the highly expressed FXYD5 in sorafenib-resistant HCC cells and its higher expression level in HCC tissues compared to par-acancerous tissues. The downregulation of FXYD5 reversed the resistance of Huh7/sora cells to sorafenib, while overexpression of FXYD5 reduced the sensitivity of HCC cells to sorafenib. Additionally, abnormal activation of the Akt/mTOR signaling pathway was found in Huh7/sora cells, and MK2206, an Akt inhibitor, increased the sensitivity of HCC cells to sorafenib. The expression level of p-Akt was positively correlated with the expression of FXYD5 in HCC tissues.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Oncology
Timothy Wai Ho Shuen, Marianna Alunni-Fabbroni, Elif Ocal, Peter Malfertheiner, Moritz Wildgruber, Regina Schinner, Maciej Pech, Julia Benckert, Bruno Sangro, Christiane Kuhl, Antonio Gasbarrini, Pierce Kah Hoe Chow, Han Chong Toh, Jens Ricke
Summary: EV-based proteomics can predict the response of patients with advanced HCC to SIRT+sorafenib and sorafenib-only treatment, providing a new approach for treatment response prediction.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Bhuwan Prasad Awasthi, Prakash Chaudhary, Diwakar Guragain, Jun-Goo Jee, Jung-Ae Kim, Byeong-Seon Jeong
Summary: Compound 6, a hybrid compound of sorafenib and 2,4,5-trimethylpyridin-3-ols, shows promising anti-proliferative activity and lower cytotoxicity compared to sorafenib in hepatocellular carcinoma. It may be a potential candidate for targeted therapy with reduced toxic side effects on normal cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Mehak Passi, Stefan Zahler
Summary: Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide, with most cases being associated with chronic liver fibrosis which leads to increased liver tissue stiffness. Changes in tissue stiffness affect mechanical signaling pathways, modulating the progression of HCC-related genes. However, mechanical signaling pathways are still less emphasized in comparison to classical biochemical signaling pathways in our understanding of cancer.