Skip Navigation
Skip to contents

Cancer Res Treat : Cancer Research and Treatment

OPEN ACCESS

Search

Page Path
HOME > Search
1 "Cathepsin C"
Filter
Filter
Article category
Keywords
Publication year
Authors
Funded articles
Original Article
Cathepsin C Interacts with TNF-α/p38 MAPK Signaling Pathway to Promote Proliferation and Metastasis in Hepatocellular Carcinoma
Guo-Pei Zhang, Xiao Yue, Shao-Qiang Li
Cancer Res Treat. 2020;52(1):10-23.   Published online April 26, 2019
DOI: https://doi.org/10.4143/crt.2019.145
AbstractAbstract PDFPubReaderePub
Purpose
Although cathepsin C (CTSC) has been reported to maintain malignant biological properties in various cancers, its functions in hepatocellular carcinoma (HCC) remain obscure. We aimed to investigate the potential role of CTSC in HCC.
Materials and Methods
HCC tissue microarrays (n=122) were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. Quantitative real-time polymerase chain reaction, western blot assay, Cell Counting Kit-8 assay, colony formation, cell migration, and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools.
Results
By bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients (hazard ratio, 2.402; 95% confidence interval, 1.493 to 3.865; p < 0.001). By gain/loss-of-function assays, we implicated that CTSC functioned as an oncogene to promote the proliferation and metastasis of HCC cells. Mechanistically, we revealed that CTSC was involved in several cancer-related signaling pathways by Gene Set Enrichment Analysis, among which tumor necrosis factor α (TNF-α)/p38 pathway was verified to be activated by CTSC. Furthermore, we found that TNF-α could activate CTSC expression in a concentration- dependent manner. Ralimetinib, an oral p38 mitogen-activated protein kinase (MAPK) inhibitor could inhibit CTSC expression. These indicated a potential positive feedback loop between CTSC and TNF-α/MAPK (p38) signaling.
Conclusion
Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.

Citations

Citations to this article as recorded by  
  • Synergistic DBNDD1–GDF15 Signaling Activates the NF-κB Pathway to Promote Colorectal Cancer Progression
    Xiaomin Qi, Caijuan Bai, Li Dong, Anqi Wang, Chaojun Wei, Yonghong Li, Mengyuan Zhao, Chongge You
    Molecular Cancer Research.2026; 24(2): 119.     CrossRef
  • Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer
    Satarupa Pradhan, Shama Prasada Kabekkodu, Sangavi Eswaran, Naveena A. N. Kumar, Dinesh Upadhya, Sanjiban Chakrabarty, Vasudha Devi
    Clinical Epigenetics.2026;[Epub]     CrossRef
  • Stefin B and Cystatin C Deficiency Suppresses Tumor Growth and Alters Tumor Microenvironment in a Breast Cancer Model
    Petra Matjan Štefin, Janja Završnik, Miha Butinar, Georgy Mikhaylov, Boris Turk, Olga Vasiljeva
    Cells.2026; 15(4): 360.     CrossRef
  • SNRPD2-mediated regulation of DDX39B splicing promotes endometrial cancer progression by suppressing the activation of CTSC cryptic exons
    Yingwei Li, Zhongshao Chen, Yanling Liu, Yuehan Gao, Yingying Pu, Qianqian Gao, Feng Gao, Ning Yang, Peng Li
    Cell Death & Disease.2026;[Epub]     CrossRef
  • CTSC Confers Radioresistance in Hepatocellular Carcinoma by Regulating Myeloid‐Derived Suppressor Cells
    Jiahuan Xu, Bilin Zhang, Shirui Yang, Shaoran Song, Jie Wu, Yunzhi Dang
    Journal of Cellular and Molecular Medicine.2026;[Epub]     CrossRef
  • Cathepsin C orchestrates RSV-induced asthma exacerbation through the dual effect of monocyte-derived macrophages
    Xizi Du, Xinyu Wu, Lin Yuan, Huaiqing Luo, Leyuan Wang, Huijun Liu, Ye Yao, Siqi Yao, Qiuyan Qin, Qianyu Zhao, Dan Liu, Yang Xiang, Xiaoqun Qin, Ming Yang, Weining Xiong, Chi Liu
    Cellular & Molecular Immunology.2026; 23(6): 719.     CrossRef
  • Targeting Cathepsin C in Cancer Metastasis: Protease Network Activation, Inflammatory Crosstalk, and Therapeutic Opportunities
    Yahui Liu, Liangyu Hao, Lixiang Zheng
    International Journal of Molecular Sciences.2026; 27(12): 5369.     CrossRef
  • Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies
    Yang Li, Jiajie Feng, Xinzhu Dong, Ziyue Yuan, Ling-Li Zheng, Lan Zhang, Lei Wang
    Biomarker Research.2026;[Epub]     CrossRef
  • Melatonin Inhibits Metastasis of Sunitinib‐Resistant Renal Cell Carcinoma Cells Via the GRP78/p38/CTSD Expression
    Po‐Yu Huang, Yi‐Hsien Hsieh, Yong‐Syuan Chen, Tung‐Wei Hung, Hui‐Ling Chiou, Pei‐Ni Chen, Chun‐Wen Cheng, Jen‐Pi Tsai
    Journal of Pineal Research.2026;[Epub]     CrossRef
  • Role of lysosomes in tumorigenesis and metastasis
    Die FAN, XinYi YAO, RuiJuan SUN, XinYi ZHOU, JianWei SUN, Nan LIU
    SCIENTIA SINICA Vitae.2025; 55(4): 742.     CrossRef
  • Cathepsin B in urological tumors: unraveling its role and therapeutic potential
    Zhaojie Yan, Guansong Zheng, Junrong Zou, Xiaofeng Zou, Keqiang Chai, Guoxi Zhang
    Discover Oncology.2025;[Epub]     CrossRef
  • Exploring therapeutic and diagnostic potential of cysteine cathepsin as targets for cancer therapy with nanomedicine
    Anil Giri, In-Sun Hong, Taeg Kyu Kwon, Jong-Sun Kang, Jee-Heon Jeong, Seho Kweon, Simmyung Yook
    International Journal of Biological Macromolecules.2025; 315: 144324.     CrossRef
  • Cathepsin C correlates with M2 macrophage infiltration and regulates the tumor growth and metastasis in non-small cell lung cancer
    Xiaoxia Tong, Ting Zhu, Li Ma, Xiaohu Yang, Chenghui Li, Yibing Liu, Xuan Qin, Yanguang Ding, Hongwei Xia, Yonglei Liu
    BMC Cancer.2025;[Epub]     CrossRef
  • Identification of CTSC-driven progression in ESCC by single-cell sequencing and experimental validation
    Xin Sui, Yongxu Jia, Jing Li, Jiayao Xu, Wenjia Wang, Yanru Qin
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • CCL20 mediates the effect of cathepsin S on hepatocellular carcinoma development insights from Mendelian randomization and bioinformatics analysis
    Chunling Yuan, Qian Li, Min luo, Chaoyong Liang, Lu Huang, Lifen Wei, Qinglin He, Zhihui Liu, Liming Shang
    Discover Oncology.2025;[Epub]     CrossRef
  • Cathepsin C-driven enhancement of neutrophil extracellular trap formation contributes to acute lung injury
    Xinyu Wu, Huijun Liu, Qingwu Qin, Lin Yuan, Ye Yao, Xizi Du, Qiuyan Qin, Leyuan Wang, Qianyu Zhao, Ling Qin, Yang Xiang, Ming Yang, Xiaoqun Qin, Chi Liu
    iScience.2025; 28(12): 113928.     CrossRef
  • A pan-cancer analysis of CTSC as a candidate prognostic and immune-related biomarker
    Lan Zheng, Xin Liu, Yiling Xi, Dacai Gong, Bin Ge, Xing Wei, Jinwen Cai, Peng Chen
    Discover Oncology.2025;[Epub]     CrossRef
  • CTSC promoted the migration and invasion of glioma cells via activation of STAT3/SERPINA3 axis
    Qi Li, Chenguang Wan, Zhifei Zhang, Guangwei Liu, Song Wang
    Gene.2024; 893: 147948.     CrossRef
  • Characterization and function analysis of cathepsin C in Marsupenaeus japonicus
    Zuhao Tu, Jian Zhong, Hongquan Li, Liangjuan Sun, Yucong Huang, Shiping Yang, Yishan Lu, Shuanghu Cai
    Fish & Shellfish Immunology.2024; 146: 109379.     CrossRef
  • Cathepsin B: The dawn of tumor therapy
    Fuxian Liu, Ting Zhou, Shangzu Zhang, Yangyang Li, Yan Chen, Zhiming Miao, Xin Wang, Gengqiang Yang, Qiyang Li, Liying Zhang, Yongqi Liu
    European Journal of Medicinal Chemistry.2024; 269: 116329.     CrossRef
  • Targeting inflammation as cancer therapy
    Manni Wang, Siyuan Chen, Xuemei He, Yong Yuan, Xiawei Wei
    Journal of Hematology & Oncology.2024;[Epub]     CrossRef
  • DNA Damage-driven Inflammatory Cytokines: Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy
    Meng-jie Wang, Yu Xia, Qing-lei Gao
    Current Medical Science.2024; 44(2): 261.     CrossRef
  • Identification of PANoptosis-related subtypes, construction of a prognosis signature, and tumor microenvironment landscape of hepatocellular carcinoma using bioinformatic analysis and experimental verification
    Guoqing Ouyang, Qiuyun Li, Yangnian Wei, Wenbin Dai, Haojian Deng, Youli Liu, Jiaguang Li, Mingjuan Li, Shunwen Luo, Shuang Li, Yunying Liang, Guandong Pan, Jianqing Yang, Tao Gan
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury
    Jing Yu, Yu Fu, Jiameng Gao, Qingqing Zhang, Nan Zhang, Zhiyuan Zhang, Xuemei Jiang, Chang Chen, Zongmei Wen
    Redox Biology.2024; 74: 103231.     CrossRef
  • Protective Effects of Hydroalcoholic Leaf Extract of Origanum Vulgare against Paraquat-induced Lung Toxicity in Rats: The Role of the Inflammation-related Markers and Oxidative Stress
    Ali Sharifi-Rigi, Esfandiar Heidarian, Fatemeh Zal
    The Natural Products Journal.2024;[Epub]     CrossRef
  • Cathepsin C regulates tumor progression via the Yes-associated protein signaling pathway in non-small cell lung cancer
    Nayoung Kim
    American Journal of Cancer Research.2024; 14(1): 97.     CrossRef
  • DOX-PLGA Nanoparticles Effectively Suppressed the Expression of Pro-Inflammatory Cytokines TNF-a, IL-6, iNOS, and IL-1β in MCF-7 Breast Cancer Cell Line
    Rawan Hassan Al-Saeedi, Mohammad Khalaj-Kondori, Mohammad Ali Hosseinpour Feizi, Jafar Hajavi
    Reports of Biochemistry and Molecular Biology.2024; 12(4): 530.     CrossRef
  • Cathepsin C in health and disease: from structural insights to therapeutic prospects
    Chakriya Chitsamankhun, Nutwara Siritongtaworn, B. P. J. Fournier, Kanokwan Sriwattanapong, Thanakorn Theerapanon, Lakshman Samaranayake, Thantrira Porntaveetus
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Cathepsin C Promotes Tumorigenesis in Bladder Cancer by Activating the Wnt/β-catenin Signalling Pathway
    Xinsheng Wang, Yong Jia, Dawen Wang
    Frontiers in Bioscience-Landmark.2024;[Epub]     CrossRef
  • Cysteine cathepsins: From diagnosis to targeted therapy of cancer
    Ana Ercegovič Rot, Matija Hrovatin, Bor Bokalj, Ernestina Lavrih, Boris Turk
    Biochimie.2024; 226: 10.     CrossRef
  • Searching for novel cellular targets for MASLD and HCC within the humble lysosomal cathepsins
    Alejandro del Castillo-Cruz, Maria Fernández-Fernández, Anna Moles
    Exploration of Digestive Diseases.2024; 3(6): 428.     CrossRef
  • Integrative multi-omics analysis reveals a novel subtype of hepatocellular carcinoma with biological and clinical relevance
    Shizhou Li, Yan Lin, Xing Gao, Dandan Zeng, Weijie Cen, Yuejiao Su, Jingting Su, Can Zeng, Zhenbo Huang, Haoyu Zeng, Shilin Huang, Minchao Tang, Xiaoqing Li, Min Luo, Zhihu Huang, Rong Liang, Jiazhou Ye
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases
    Kexin Zhao, Yangqing Sun, Shangwei Zhong, Jun-Li Luo
    Biomarker Research.2024;[Epub]     CrossRef
  • Exploring the potential targets of the Abrus cantoniensis Hance in the treatment of hepatitis E based on network pharmacology
    Ziheng Xu, Can Wang, Zuxiang Luan, Dapei Zhang, Baiqing Dong
    Frontiers in Veterinary Science.2023;[Epub]     CrossRef
  • Characterization, Potential Prognostic Value, and Immune Heterogeneity of Cathepsin C in Diffuse Glioma
    Quanwei Zhou, Shasha Li, Xuejun Yan, Hecheng Zhu, Weidong Liu, Youwei Guo, Hongjuan Xu, Wen Yin, Xuewen Li, Qian Yang, Hui Liu, Xingjun Jiang, Caiping Ren
    Current Bioinformatics.2023; 18(1): 76.     CrossRef
  • Correlation Analysis of CTSB Promoter Polymorphism and Function in Patients with Dilated Cardiomyopathy
    Yu Zhou, Shuang Gao, Liangcai Ding, Han Yan, Shuchao Pang, Bo Yan
    DNA and Cell Biology.2023; 42(4): 203.     CrossRef
  • The role of cytokines in the pathogenesis of malignant neoplasms
    V. L. Rybkina, G. V. Adamova, D. S. Oslina
    Сибирский научный медицинский журнал.2023; 43(2): 15.     CrossRef
  • The role of lysosomal peptidases in glioma immune escape: underlying mechanisms and therapeutic strategies
    Hao Liu, Jie Peng, Linzhen Huang, Dong Ruan, Yuguang Li, Fan Yuan, Zewei Tu, Kai Huang, Xingen Zhu
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Cathepsin C: structure, function, and pharmacological targeting
    Milena Stojkovska Docevska, Marko Novinec
    Rare Disease and Orphan Drugs Journal.2023;[Epub]     CrossRef
  • Longitudinal Serum Proteomics Characterization of CD19-CAR-T Cell Therapy for B-Cell Malignancies
    Youming Wang, Rui Sun, Weigang Ge, Lei Xue, Qianwen Xu, Hui Xu, Sujun Li, Miaomiao Wu, Tiannan Guo, Xingbing Wang
    Journal of Proteome Research.2023; 22(9): 2985.     CrossRef
  • The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer
    Veronika Stoka, Olga Vasiljeva, Hiroshi Nakanishi, Vito Turk
    International Journal of Molecular Sciences.2023; 24(21): 15613.     CrossRef
  • The Role of Cytokines in the Pathogenesis of Malignant Neoplasms
    V. L. Rybkina, G. V. Adamova, D. S. Oslina
    Cell and Tissue Biology.2023; 17(6): 608.     CrossRef
  • Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease
    James D. Chalmers, Ralph Kettritz, Brice Korkmaz
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Nanoparticle-based drug delivery systems in cancer: A focus on inflammatory pathways
    Amir R. Afshari, Mehdi Sanati, Hamid Mollazadeh, Prashant Kesharwani, Thomas P. Johnston, Amirhossein Sahebkar
    Seminars in Cancer Biology.2022; 86: 860.     CrossRef
  • Cysteine cathepsin C: a novel potential biomarker for the diagnosis and prognosis of glioma
    Xingbo Cheng, Zhishuai Ren, Zhendong Liu, Xiang Sun, Rongjun Qian, Chen Cao, Binfeng Liu, Jialin Wang, Hongbo Wang, Yuqi Guo, Yanzheng Gao
    Cancer Cell International.2022;[Epub]     CrossRef
  • Lysosomal peptidases—intriguing roles in cancer progression and neurodegeneration
    Janko Kos, Ana Mitrović, Milica Perišić Nanut, Anja Pišlar
    FEBS Open Bio.2022; 12(4): 708.     CrossRef
  • Regulatory T-cells-related signature for identifying a prognostic subtype of hepatocellular carcinoma with an exhausted tumor microenvironment
    Genhao Zhang
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma
    Zhao-Shan Niu, Wen-Hong Wang, Xiao-Jun Niu
    World Journal of Gastroenterology.2022; 28(46): 6433.     CrossRef
  • Construction and validation of prognostic signature for hepatocellular carcinoma basing on hepatitis B virus related specific genes
    Lei Wang, Manman Qiu, Lili Wu, Zexing Li, Xinyi Meng, Lu He, Bing Yang
    Infectious Agents and Cancer.2022;[Epub]     CrossRef
  • Identification of new potential antigen recognized by γδT cells in hepatocellular carcinoma
    Xueyan Xi, Yang Guo, Min Zhu, Fen Qiu, Feifei Lei, Gang Li, Boyu Du
    Cancer Immunology, Immunotherapy.2021; 70(7): 1917.     CrossRef
  • Inflammatory Cytokines in Cancer: Comprehensive Understanding and Clinical Progress in Gene Therapy
    Tianxia Lan, Li Chen, Xiawei Wei
    Cells.2021; 10(1): 100.     CrossRef
  • Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy
    María Florencia Mercogliano, Sofía Bruni, Florencia Mauro, Patricia Virginia Elizalde, Roxana Schillaci
    Cancers.2021; 13(3): 564.     CrossRef
  • Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice
    Ekaterina O. Gubernatorova, Almina I. Polinova, Mikhail M. Petropavlovskiy, Olga A. Namakanova, Alexandra D. Medvedovskaya, Ruslan V. Zvartsev, Georgij B. Telegin, Marina S. Drutskaya, Sergei A. Nedospasov
    Cancers.2021; 13(8): 1775.     CrossRef
  • Resveratrol inhibited the metastatic behaviors of cisplatin‐resistant human oral cancer cells via phosphorylation of ERK/p‐38 and suppression of MMP‐2/9
    Wen‐Shin Chang, Chia‐Wen Tsai, Jai‐Sing Yang, Yuan‐Man Hsu, Liang‐Chun Shih, Hong‐Yi Chiu, Da‐Tian Bau, Fuu‐Jen Tsai
    Journal of Food Biochemistry.2021;[Epub]     CrossRef
  • Identifying Dendritic Cell–Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis
    Chaoyuan Huang, Xiaotao Jiang, Yuancheng Huang, Lina Zhao, Peiwu Li, Fengbin Liu
    Frontiers in Molecular Biosciences.2021;[Epub]     CrossRef
  • Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis
    Apriliana E. R. Kartikasari, Cesar S. Huertas, Arnan Mitchell, Magdalena Plebanski
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • The multifaceted role of cathepsins in liver disease
    Paloma Ruiz-Blázquez, Valeria Pistorio, María Fernández-Fernández, Anna Moles
    Journal of Hepatology.2021; 75(5): 1192.     CrossRef
  • Aging-related genes are potential prognostic biomarkers for patients with gliomas
    Gelei Xiao, Xiangyang Zhang, Xun Zhang, Yuanbing Chen, Zhiwei Xia, Hui Cao, Jun Huang, Quan Cheng
    Aging.2021; 13(9): 13239.     CrossRef
  • Cathepsin C inhibitors as anti-inflammatory drug discovery: Challenges and opportunities
    Xiao Bao Shen, Xing Chen, Zhao Yan Zhang, Fu Fang Wu, Xin Hua Liu
    European Journal of Medicinal Chemistry.2021; 225: 113818.     CrossRef
  • Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death
    Jialin Dai, Jiangjin Liu, Qiong Zhang, Yang An, Bing Xia, Changwu Wan, Yuanyuan Zhang, Yanni Yu, Jie Wang, Hangang Yu
    Cardiovascular Therapeutics.2021; 2021: 1.     CrossRef
  • Cathepsin C inhibition as a potential treatment strategy in cancer
    Brice Korkmaz, Anne-Sophie Lamort, Roxane Domain, Céline Beauvillain, Artur Gieldon, Ali Önder Yildirim, Georgios T. Stathopoulos, Moez Rhimi, Dieter E. Jenne, Ralph Kettritz
    Biochemical Pharmacology.2021; 194: 114803.     CrossRef
  • Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution
    Jun Pan, Fang Ye, Chengxuan Yu, Qinsheng Zhu, Jiaqi Li, Yaohui Zhang, Hedi Tian, Yunjin Yao, Minjie Zhu, Yibin Shen, Feng Zhu, Yingying Wang, Xinhui Zhou, Guoji Guo, Yijun Wu
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
  • In Silico Comparative Studies of Tumor Necrosis Factor Alpha-Induced Proteins
    Sri Venkata Anandavalli Nallapati#, Manasa Reddy Sanaga#, Swapna Aedhu#, Naga Harini Parimi, Shravan Kumar Gunda
    International Journal Of Pharmaceutical And Phytopharmacological Research.2021; 11(6): 21.     CrossRef
  • Praeruptorin B Mitigates the Metastatic Ability of Human Renal Carcinoma Cells through Targeting CTSC and CTSV Expression
    Chia-Liang Lin, Tung-Wei Hung, Tsung-Ho Ying, Chi-Jui Lin, Yi-Hsien Hsieh, Chien-Min Chen
    International Journal of Molecular Sciences.2020; 21(8): 2919.     CrossRef
  • 15,010 View
  • 429 Download
  • 65 Web of Science
  • 64 Crossref
Close layer

Cancer Res Treat : Cancer Research and Treatment
Close layer
TOP