TM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes

Cited 13 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorH Sun-
dc.contributor.authorE Kim-
dc.contributor.authorJ Ryu-
dc.contributor.authorH Lee-
dc.contributor.authorE A Shin-
dc.contributor.authorM Lee-
dc.contributor.authorH Lee-
dc.contributor.authorJ H Lee-
dc.contributor.authorJ H Yoon-
dc.contributor.authorD G Song-
dc.contributor.authorSemi Kim-
dc.contributor.authorJ W Lee-
dc.date.accessioned2022-01-14T15:31:31Z-
dc.date.available2022-01-14T15:31:31Z-
dc.date.issued2022-
dc.identifier.issn1420-682X-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/25272-
dc.description.abstractAberrant extracellular matrix and immune cell alterations within the tumor microenvironment promote the pathological progression of liver carcinogenesis. Although transmembrane 4 L six family member 5 (TM4SF5) is involved in liver fibrosis and cancer, its mechanism avoiding immune surveillance during carcinogenesis remains unknown. We investigated how TM4SF5-mediated signaling caused immune evasion using in vitro primary cells and in vivo liver tissues from genetic or chemically induced mouse models. TM4SF5-transgenic and diethylnitrosamine (DEN)-induced liver cancer mouse models exhibited fibrotic and cancerous livers, respectively, with enhanced TM4SF5, pY705STAT3, collagen I, and laminin γ2 levels. These TM4SF5-mediated effects were abolished by TM4SF5 inhibitor, 4'-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC). TM4SF5-dependent tumorigenesis involved natural killer (NK) cell exhaustion-like phenotypes including the reduction of NK cell number or function, which were blocked with TSAHC treatment. TM4SF5 expression in cancer cells downregulated stimulatory ligands and receptors for NK cell cytotoxicity, including SLAMF6, SLAMF7, MICA/B, and others. TM4SF5 suppression or inhibition reduced STAT3 signaling activity and recovered the receptor levels and NK cell surveillance, leading to reduced fibrotic and cancerous phenotypes, and longer survival. Altogether, these findings suggest that TM4SF5-mediated STAT3 activity for extracellular matrix modulation is involved in the progression of liver disease to HCC and that TM4SF5 appears to suppress NK cells during liver carcinogenesis.-
dc.publisherSpringer-
dc.titleTM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes-
dc.title.alternativeTM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes-
dc.typeArticle-
dc.citation.titleCellular and Molecular Life Sciences-
dc.citation.number1-
dc.citation.endPage49-
dc.citation.startPage49-
dc.citation.volume79-
dc.contributor.affiliatedAuthorSemi Kim-
dc.contributor.alternativeName선현승-
dc.contributor.alternativeName김은미-
dc.contributor.alternativeName류지혜-
dc.contributor.alternativeName이혜진-
dc.contributor.alternativeName신은애-
dc.contributor.alternativeName이민형-
dc.contributor.alternativeName이해송-
dc.contributor.alternativeName이정훈-
dc.contributor.alternativeName윤정환-
dc.contributor.alternativeName송대근-
dc.contributor.alternativeName김세미-
dc.contributor.alternativeName이정원-
dc.identifier.bibliographicCitationCellular and Molecular Life Sciences, vol. 79, no. 1, pp. 49-49-
dc.identifier.doi10.1007/s00018-021-04051-x-
dc.subject.keywordImmune checkpoint-
dc.subject.keywordNK cell immune therapy · Liver cancer · Signal transduction-
dc.subject.keywordL6 family member-
dc.subject.localImmune checkpoint-
dc.subject.localimmune checkpoint-
dc.subject.localNK cell immune therapy · Liver cancer · Signal transduction-
dc.subject.localL6 family member-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.