|Table of Contents|

Research progress on the role of stefins in tumorigenesis and development

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 05
Page:
978-982
Research Field:
Publishing date:

Info

Title:
Research progress on the role of stefins in tumorigenesis and development
Author(s):
LIN Yangyuan1; 2
1.Basic Medical College,Putian University,Fujian Putian 351100,China;2.Key Laboratory of Translational Cancer Research of Fujian Province University,Putian University,Fujian Putian 351100,China.
Keywords:
stefins; tumor; cathepsin; biomarker; prognosis
PACS:
R730.54
DOI:
10.3969/j.issn.1672-4992.2024.05.034
Abstract:
stefins is a subfamily of cystatin superfamily,which apparently acts as endogenous inhibitors of cathepsins,belonging to type I cystatins.stefins has many biological functions:Stefins has been shown to be implicated in the balance of proteolysis,catabolism of proteins,proliferation and apoptosis.stefins also has been reported to play an important function on cell differentiation,infection and immunity,angiogenesis and tumor cell invasion and metastasis.The homeostatic imbalance between stefins and cathepsins was reported to be one of the most important mechanisms of tumor progression.Furthermore,some other possible mechanisms responsible for involving tumorigenesis by stefins have been reported to be mediated by cathepsin-independent pathway.In this article,the current progress in the role of stefins and the molecular mechanisms underlying the altered regulation of stefins in cancer are summarized.Besides,we also review recent advances of stefins acting as diagnostic or prognostic markers in distinctive cancers.

References:

［1］OCHIENG J,CHAUDHURI G.Cystatin superfamily［J］.J Health Care Poor Underserved,2010,21(1 Suppl):51-70.
［2］SHANNON P,PENNACCHIO LA,HOUSEWEART MK,et al.Neuropathological changes in a mouse model of progressive myoclonus epilepsy:cystatin B deficiency and unverricht-lundborg disease［J］.J Neuropathol Exp Neurol,2002,61(12):1085-1091.
［3］HSIEH WT,FONG D,SLOANE BF,et al.Mapping of the gene for human cysteine proteinase inhibitor stefin A,STF1,to chromosome 3cen-q21［J］.Genomics,1991,9(1): 207-209.
［4］RITONJA A,MACHLEIDT W,BARRETT AJ.Amino acid sequence of the intracellular cysteine proteinase inhibitor cystatin B from human liver［J］.Biochem Biophys Res Commun,1985,131(3):1187-1192.

［5］ZAMYATNIN AA JR,GREGORY LC,TOWNSEND PA,et al.Beyond basic research:the contribution of cathepsin B to cancer development,diagnosis and therapy［J］.Expert Opin Ther Targets,2022,26(11):963-977.
［6］BREZNIK B,MITROVIＣ A,LAH TT,et al.Cystatins in cancer progression:More than just cathepsin inhibitors［J］.Biochimie,2019,166:233-250.
［7］WERLE B,SCHANZENBCHER U,LAH TT,et al.Cystatins in non-small cell lung cancer:tissue levels,localization and relation to prognosis［J］.Oncol Rep,2006,16(4):647-655.
［8］STROJAN P,BUDIHNA M,SMID L,et al.Prognostic significance of cysteine proteinases cathepsins B and L and their endogenous inhibitors stefins A and B in patients with squamous cell carcinoma of the head and neck［J］.Clin Cancer Res,2000,6(3):1052-1062.
［9］LI C,CHEN L,WANG J,et al.Expression and clinical significance of cathepsin B and stefin A in laryngeal cancer［J］.Oncol Rep,2011,26(4):869-875.
［10］LI W,DING F,ZHANG L,et al.Overexpression of stefin A in human esophageal squamous cell carcinoma cells inhibits tumor cell growth,angiogenesis,invasion,and metastasis［J］.Clin Cancer Res,2005,11(24 Pt 1):8753-8762.
［11］CHANG SH,KANASAKI K,GOCHEVA V,et al.VEGF-A induces angiogenesis by perturbing the cathepsin-cysteine protease inhibitor balance in venules,causing basement membrane degradation and mother vessel formation［J］.Cancer Res,2009,69(10):4537-4544.
［12］刘彪，范奇超，林扬元，等.半胱氨酸蛋白酶抑制剂 stefins 的功能研究进展［J］.解放军医学院学报,2015,36(5): 518-520. LIU B，FAN QC，LIN YY，et al.Advances in biological function of stefins［J］.Acad J Chin PLA Med Sch,2015,36(5): 518-520.
［13］BERVAR A,ZAJC I,SEVER N,et al.Invasiveness of transformed human breast epithelial cell lines is related to cathepsin B and inhibited by cysteine proteinase inhibitors［J］.Biol Chem,2003,384(3):447-455.
［14］DUIVENVOORDEN HM,RAUTELA J,EDGINGTON-MITCHELL LE,et al.Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion［J］.J Pathol,2017,243(4):496-509.
［15］ZHANG J,SHI Z,HUANG J,et al.CSTB downregulation promotes cell proliferation and migration and suppresses apoptosis in gastric cancer SGC-7901 cell line［J］.Oncol Res,2016,24(6):487-494.
［16］MA Y,CHEN Y,LI Y,et al.Cystatin A suppresses tumor cell growth through inhibiting epithelial to mesenchymal transition in human lung cancer［J］.Oncotarget,2017,9(18):14084-14098.
［17］JOHN MARY DJS,MANJEGOWDA MC,KUMAR A,et al.The role of cystatin A in breast cancer and its functional link with ERalpha［J］.J Genet Genomics,2017,44(12):593-597.
［18］LIU ZJ,ZHENG LS,LI CZ,et al.Correlated with better prognosis,CSTA inhibits metastasis of nasopharyngeal carcinoma cells via suppressing AKT signaling through promoting METTL3 degradation［J］.Biochim Biophys Acta Mol Basis Dis,2023,1869(5):166696.
［19］GOLE B,HUSZTHY PC,POPOVIСM,et al.The regulation of cysteine cathepsins and cystatins in human gliomas［J］.Int J Cancer,2012,131(8):1779-1789.
［20］ZAJC I,SEVER N,BERVAR A,et al.Expression of cysteine peptidase cathepsin L and its inhibitors stefins A and B in relation to tumorigenicity of breast cancer cell lines［J］.Cancer Lett,2002,187(1-2):185-190.
［21］RUDZINSKA-RADECKA M,FROLOVA AS,BALAKIREVA AV,et al.In silico,in vitro,and clinical investigations of cathepsin B and stefin A mRNA expression and a correlation analysis in kidney cancer［J］.Cells,2022,11(9):1455.
［22］LIN YY,CHEN ZW,LIN ZP,et al.Tissue levels of stefin A and stefin B in hepatocellular carcinoma［J］.Anat Rec (Hoboken),2016,299(4):428-438.
［23］SHIBA D,TERAYAMA M,YAMADA K,et al.Clinicopathological significance of cystatin A expression in progression of esophageal squamous cell carcinoma［J］.Medicine (Baltimore),2018,97(15):e0357.
［24］WANGX,GUI L,ZHANG Y,et al.Cystatin B is progression marker of human epithelial ovarian tumors mediated by the TGF-beta signaling pathway［J］.Int J Oncol,2014,44(4):1099-1106.
［25］GUAN W,WANG X,LIN Q,et al.Transforming growth factor-beta/miR-143-3p/cystatin B axis is a therapeutic target in human ovarian cancer［J］.Int J Oncol,2019,55(1):267-276.
［26］YANG F,TAY KH,DONG L,et al.Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIP(L) from degradation by the E3 ligase itch in human melanoma cells［J］.Cell Death Differ,2010,17(8):1354-1367.
［27］BUTINAR M,PREBANDA MT,RAJKOVIС J,et al.stefin B deficiency reduces tumor growth via sensitization of tumor cells to oxidative stress in a breast cancer model［J］.Oncogene,2014,33(26):3392-3400.
［28］SUN T,TURK V,TURK B,et al.Increased expression of stefin B in the nucleus of T98G astrocytoma cells delays caspase activation［J］.Front Mol Neurosci,2012,5:93.
［29］JIANG Y,HAN L,XUE M,et al.Cystatin B increases autophagic flux by sustaining proteolytic activity of cathepsin B and fuels glycolysis in pancreatic cancer:CSTB orchestrates autophagy and glycolysis in PDAC［J］.Clin Transl Med,2022,12:e1126.
［30］谢群,林丽彬,张金添,等.stefin B调控巨噬细胞极化对肝癌细胞增殖、迁移、侵袭及上皮间质转化的影响［J］.西安交通大学学报(医学版),2020,41(4): 530-538. XIE Q,LIN LB,ZHANG JT,et al.Effects of polarized macrophages regulated by stefin B on proliferation,migration,invasion and epithelial-mesenchymal transition of hepatoma carcinoma cells［J］.Journal of Xi'an Jiaotong University(Medical Sciences),2020,41(4):530-538.
［31］谢群,林丽彬,张金添,等.体内外共培养体系中肝癌细胞对肝星状细胞活化的影响［J］.西安交通大学学报(医学版),2019,40(2): 227-234. XIE Q,LIN LB,ZHANG JT,et al.Activation of hepaticstellate cells cocultured with hepatoma carcinoma cells in vitro and in vivo ［J］.Journal of Xi'an Jiaotong University(Medical Sciences),2019,40(2): 227-234.
［32］LEE MJ,YU GR,PARK SH,et al.Identification of cystatin B as a potential serum marker in hepatocellular carcinoma［J］.Clin Cancer Res,2008,14(4): 1080-1089.
［33］ANIIN A,GALE N,SMID L,et al.Expression of stefin A is of prognostic significance in squamous cell carcinoma of the head and neck［J］.Eur Arch Otorhinolaryngol,2013,270(12): 3143-3151.
［34］SINHA AA,QUAST BJ,WILSON MJ,et al.Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma［J］.Cancer,2002,94(12): 3141-3149.
［35］CHANG KP,WU CC,CHEN HC,et al.Identification of candidate nasopharyngeal carcinoma serum biomarkers by cancer cell secretome and tissue transcriptome analysis: potential usage of cystatin A for predicting nodal stage and poor prognosis［J］.Proteomics,2010,10(14): 2644-2660.
［36］KOMURA T,TAKABATAKE H,HARADA K,et al.Clinical features of cystatin A expression in patients with pancreatic ductal adenocarcinoma［J］.Cancer Sci,2017,108(11): 2122-2129.
［37］DOHM A,SU J,MCTYRE ER,et al.Identification of CD37,cystatin A,and IL-23A gene expression in association with brain metastasis: analysis of a prospective trial［J］.Int J Biol Markers,2019,34(1): 90-97.
［38］MA Y,CHEN Y,PETERSEN I.Expression and epigenetic regulation of cystatin B in lung cancer and colorectal cancer［J］.Pathol Res Pract,2017,213(12): 1568-1574.
［39］WANG Y,WANG L,LI X,et al.Decreased CSTA expression promotes lymphatic metastasis and predicts poor survival in oral squamous cell carcinoma［J］.Arch Oral Biol,2021,126:105116.
［40］KOOPAIE M,GHAFOURIAN M,MANIFAR S,et al.Evaluation of CSTB and DMBT1 expression in saliva of gastric cancer patients and controls［J］.BMC Cancer,2022,22(1):473.
［41］HUANG C,AI X,HU L,et al.The role of NMP22 and CSTB levels in predicting postoperative recurrence of bladder cancer［J］.J Immunol Res,2022,2022:6735310.

Memo

Memo:
National Natural Science Foundation of China（No.81201670）;国家自然科学基金(编号：81201670)；福建省自然科学基金(编号：2017J01546)
Last Update: 2024-01-30