中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 4
Apr.  2020
Turn off MathJax
Article Contents

STAT3: A key molecule in the progression of liver cancer mediated by chronic inflammation

DOI: 10.3969/j.issn.1001-5256.2020.04.054
Research funding:

 

  • Published Date: 2020-04-20
  • STAT3,a member of the signal transducer and activator of transcription family,is abnormally activated in chronic inflammation-related tumors including liver cancer. As a key signal molecule in the microenvironment of liver cancer and inflammation,STAT3 not only participates in the inflammation-cancer transformation during the development of liver cancer,but also promotes the proliferation,invasion,and metastasis of hepatoma cells through many ways,and therefore,it may be a potential target for the treatment of liver cancer. This article reviews the recent advances in the association between STAT3 and liver cancer.

     

  • loading
  • [1] YU H,LEE H,HERMANN A,et al. Revisiting STAT3 signalling in cancer:New and unexpected biological functions[J]. Nat Rev Cancer,2014,14(11):736-746.
    [2] YU H,PARDOLL D,JOVE R. STATs in cancer inflammation and immunity:A leading role for STAT3[J]. Nat Rev Cancer,2009,9(11):798-809.
    [3] AIGNER P,JUST V,STOIBER D. STAT3 isoforms:Alternative fates in cancer?[J]. Cytokine,2019,118:27-34
    [4] HEVEHAN DL,MILLER WM,PAPOUTSAKIS ET. Differential expression and phosphorylation of distinct STAT3 proteins during granulocytic differentiation[J]. Blood,2002,99(5):1627-1637.
    [5] ZHANG HF,CHEN Y,WU C,et al. The opposing function of STAT3 as an oncoprotein and tumor suppressor is dictated by the expression status of STAT3 beta in esophageal squamous cell carcinoma[J]. Clin Cancer Res,2016,22(3):691-703.
    [6] HENDRY L,JOHN S. Regulation of STAT signalling by proteolytic processing[J]. Eur J Biochem,2004,271(23-24):4613-4620.
    [7] GOU ZP,WANG DS,ZHOU L,et al. STAT3 protein expression profile and its clinical significance in hepatocellular carcinoma[J]. J Clin Hepatol,2016,29(7):520-524.(in Chinese)苟泽鹏,王德盛,周亮,等.STAT3蛋白在肝癌组织中的表达及临床意义[J].临床肝胆病杂志,2016,29(7):520-524.
    [8] XIONG S,WANG R,CHEN Q,et al. Cancer-associated fibroblasts promote stem cell-like properties of hepatocellular carcinoma cells through IL-6/STAT3/Notch signaling[J].Am J Cancer Res,2018,8(2):302-316.
    [9] LU X,WO G,LI B,et al. The anti-inflammatory NHE-06 restores antitumor immunity by targeting NF-κB/IL-6/STAT3signaling in hepatocellular carcinoma[J]. Biomed Pharmacother,2018,102:420-427.
    [10] ZHENG H,YANG Y,HAN J,et al. TMED3 promotes hepatocellular carcinoma progression via IL-11/STAT3 signaling[J]. Sci Rep,2016,6(1):37070.
    [11] PENG S,CHEN Y,GONG Y,et al. Predictive value of intratumour inflammatory cytokine mRNA levels of hepatocellular carcinoma patients and activation of two distinct pathways govern IL-8 induced epithelial-mesenchymal transition in human hepatic cancer cell lines[J]. Cytokine,2019,119:81-89.
    [12] LEI G,CHEN L,PENG M,et al. Stat3-m TOR signaling mediates the stimulation of GLP-1 production induced by IL-27[J]. J Mol Endocrinol,2019,63(3):215-226.
    [13] JING Y,SUN K,LIU W,et al. Tumor necrosis factor-alpha promotes hepatocellular carcinogenesis through the activation of hepatic progenitor cells[J]. Cancer Lett,2018,434:22-32.
    [14] KABEL AM,ALZAHRANI AA,BAWAZIR NM,et al. Targeting the proinflammatory cytokines,oxidative stress,apoptosis and TGF-beta1/STAT-3 signaling by irbesartan to ameliorate doxorubicin-induced hepatotoxicity[J]. J Infect Chemother,2018,24(8):623-631.
    [15] CHEN JX,WU YF,LI SJ,et al. 10-gingerol inhibits proliferation of hepatocellular carcinoma HepG2 cells via Src/STAT3 signaling pathway[J]. J South Med Univ,2018,38(8):1002-1007.(in Chinese)陈建新,吴依芬,李树基,等.10-姜酚通过Src/STAT3信号通路抑制肝癌HepG2细胞增殖[J].南方医科大学学报,2018,38(8):1002-1007.
    [16] EIRING AM,PAGE BDG,KRAFT IL,et al. Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy-resistant chronic myeloid leukemia[J]. Leukemia,2015,29(3):586-597.
    [17] DONG T,YAN Y,CHAI H,et al. Pyruvate kinase M2 affects liver cancer cell behavior through up-regulation of HIF-1αand Bcl-xL in culture[J]. Biomed Pharmacother,2015,69:277-284.
    [18] MO Y,HE L,LAI Z,et al. LINC01287/miR-298/STAT3 feedback loop regulates growth and the epithelial-to-mesenchymal transition phenotype in hepatocellular carcinoma cells[J].J Exp Clin Cancer Res,2018,37(1):149.
    [19] WANG S,ZHANG S,HE Y,et al. HOXA11-AS regulates JAK-STAT pathway by miR-15a-3p/STAT3 axis to promote the growth and metastasis in liver cancer[J]. J Cell Biochem,2019,120(9):15941-15951.
    [20] LI O,LI Z,TANG Q,et al. Long stress induced non-coding transcripts 5(LSINCT5)promotes hepatocellular carcinoma progression through interaction with high-mobility group AThook 2 and MiR-4516[J]. Med Sci Monit,2018,24:8510-8523.
    [21] HANAHAN D,WEINBERG RA. Hallmarks of cancer:The next generation[J]. Cell,2011,144(5):646-674.
    [22] BERASAIN C,CASTILLO J,PERUGORRIA MJ,et al. Inflammation and liver cancer:New molecular links[J]. Ann N Y Acad Sci,2009,1155(1):206-221.
    [23] XIE J,ZHANG Y,ZHANG Q,et al. Interaction of signal transducer and activator of transcription 3 polymorphisms with hepatitis B virus mutations in hepatocellular carcinoma[J]. Hepatology,2013,57(6):2369-2377.
    [24] SUN C,LAN P,HAN Q,et al. Oncofetal gene SALL4 reactivation by hepatitis B virus counteracts miR-200c in PD-L1-induced T cell exhaustion[J]. Nat Commun,2018,9(1):1241.
    [25] ZHENG Y,MING P,ZHU C,et al. Hepatitis B virus X protein-induced SH2 domain-containing 5(SH2D5)expression promotes hepatoma cell growth via an SH2D5-transketolase interaction[J]. J Biol Chem,2019,294(13):4815-4827.
    [26] GEE MS,KANG SB,KIM N,et al. Bardoxolone methyl suppresses hepatitis B virus large surface protein variant W4Prelated carcinogenesis and hepatocellular carcinoma cell proliferation via the inhibition of signal transducer and activator of transcription 3 signaling[J]. Pharmacology,2018,102(1-2):105-113.
    [27] LIU Y,FENG J SUN M,et al. Long non-coding RNA HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related hepatocellular carcinoma[J]. Cancer Lett,2019,454:158-170.
    [28] KONG L,LI S,YU X,et al. Hepatitis C virus and its protein NS4B activate the cancer-related STAT3 pathway via the endoplasmic reticulum overload response[J]. Arch Virol,2016,161(8):2149-2159.
    [29] YUAN D,HUANG S,BERGER E,et al. Kupffer cell-derived TNF triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS[J]. Cancer Cell,2017,31(6):771-789.
    [30] LIANG S,MA HY,ZHONG Z,et al. NADPH Oxidase 1 in liver macrophages promotes inflammation and tumor development in mice[J]. Gastroenterology,2019,156(4):1156-1172.
    [31] XIE JL,ZHUO SY. Role of vimentin in progression and apoptosis of primary liver cancer[J]. China Cancer,2017,26(2):130-134.(in Chinese)谢金玲,卓少元.Vimentin在原发性肝癌发生发展及凋亡过程中的作用[J].中国肿瘤,2017,26(2):130-134.
    [32] WU Y,DIAB I,ZHANG X,et al. Stat3 enhances vimentin gene expression by binding to the antisilencer element and interacting with the repressor protein,ZBP-89[J]. Oncogene,2004,23(1):168-178.
    [33] SHIN S,SUNG BJ,CHO YS,et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7[J].Biochemistry,2001,40(4):1117-1123.
    [34] ZHUO SY,XIE JL. Effect of serum containing Jianpi Yiqi decoction on MHCC-97H cell apoptosis via Caspase-3/Vimentin[J]. Chin J Exp Med Formul,2016,22(24):161-166.(in Chinese)卓少元,谢金玲.健脾益气方含药血清通过Caspase-3/Vimentin促进人肝癌MHCC-97H细胞凋亡[J].中国实验方剂学杂志,2016,22(24):161-166.
    [35] YU M,XUE H,WANG Y,et al. miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated m TOR/STAT3/AKT pathway in hepatocellular carcinoma[J]. Int J Oncol,2017,50(3):975-983.
    [36] GONG QZ,XIAO D,FENG F,et al. ent-Sauchinone as potential anticancer agent inhibiting migration and invasion of human liver cancer cells via suppressing the STAT3 signaling pathway[J]. Chem Biodivers,2018,15(4):e1800024.
    [37] LU X,KONG L,WANG X,et al. 17betahydroxysteroid dehydrogenase 4 induces liver cancer proliferationassociated genes via STAT3 activation[J]. Oncol Rep,2019,41(3):2009-2019.
    [38] WANG JR,LUO YH,PIAO XJ,et al. Mechanisms underlying isoliquiritigenin-induced apoptosis and cell cycle arrest via ROS-mediated MAPK/STAT3/NF-κB pathways in human hepatocellular carcinoma cells[J]. Drug Dev Res,2019,80(4):461-470.
    [39] YANG XM,CAO XY,HE P,et al. Overexpression of Rac GTPase activating protein 1 contributes to proliferation of cancer cells by reducing hippo signaling to promote cytokinesis[J].Gastroenterology,2018,155(4):1233-1249.
    [40] ZHOU Q,JIANG H,ZHANG J,et al. Uridine-cytidine kinase2 promotes metastasis of hepatocellular carcinoma cells via the Stat3 pathway[J]. Cancer Manag Res,2018,10:6339-6355.
    [41] HUANG B,HUANG M,LI Q. MiR-137 suppresses migration and invasion by targeting EZH2-STAT3 signaling in human hepatocellular carcinoma[J]. Pathol Res Pract,2018,214(12):1980-1986.
    [42] PAN L,XIAO H,LIAO R,et al. Fatty acid binding protein 5promotes tumor angiogenesis and activates the IL6/STAT3/VEGFA pathway in hepatocellular carcinoma[J]. Biomed Pharmacother,2018,106:68-76.
    [43] WANG Z,LI J,XIAO W,et al. The STAT3 inhibitor S3I-201suppresses fibrogenesis and angiogenesis in liver fibrosis[J].Lab Invest,2018,98(12):1600-1613.
    [44] LI Y,WANG R,XIONG S,et al. Cancer-associated fibroblasts promote the stemness of CD24(+)liver cells via paracrine signaling[J]. J Mol Med(Berl),2019,97(2):243-255.
    [45] WANG Y,WU G,FU X,et al. Aquaporin 3 maintains the stemness of CD133+hepatocellular carcinoma cells by activating STAT3[J]. Cell Death Dis,2019,10(6):465.
    [46] ZHANG K,CHE S,PAN C,et al. The SHH/Gli axis regulates CD90-mediated liver cancer stem cell function by activating the IL6/JAK2 pathway[J]. J Cell Mol Med,2018,22(7):3679-3690.
    [47] BI YH,HAN WQ,LI RF,et al. Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions[J]. World J Gastroenterol,2019,25(16):1936-1949.
    [48] WANG C,YANG M,ZHAO J,et al. Bile salt(glycochenodeoxycholate acid)induces cell survival and chemoresistance in hepatocellular carcinoma[J]. J Cel Physiol,2019,7:10899-10906.
    [49] PAN X,WANG C,LI Y,et al. Protective autophagy induced by physcion suppresses hepatocellular carcinoma cell metastasis by inactivating the JAK2/STAT3 Axis[J]. Life Sci,2018,214:124-135.
    [50] ZHANG X,ZHANG S,SUN Q,et al. Compound K induces endoplasmic reticulum stress and apoptosis in human liver cancer cells by regulating STAT3[J]. Molecules,2018,23(6):1482.
    [51] CHENG Y,LI H,DENG Y,et al. Cancer-associated fibroblasts induce PDL1+neutrophils through the IL6-STAT3pathway that foster immune suppression in hepatocellular carcinoma[J]. Cell Death Dis,2018,9(4):422.
    [52] THORN M,GUHA P,CUNETTA M,et al. Tumor-associated GM-CSF overexpression induces immunoinhibitory molecules via STAT3 in myeloid-suppressor cells infiltrating liver metastases[J]. Cancer Gene Ther,2016,23(6):188-198.
    [53] GUHA P,GARDELL J,DARPOLOR J,et al. STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells[J]. Oncogene,2019,38(4):533-548.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (890) PDF downloads(357) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return