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High membrane expression of CMTM6 in hepatocellular carcinoma is associated with tumor recurrence.
- Source :
-
Cancer science [Cancer Sci] 2021 Aug; Vol. 112 (8), pp. 3314-3323. Date of Electronic Publication: 2021 Jun 29. - Publication Year :
- 2021
-
Abstract
- CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) maintains membrane PD-L1 expression by controlling its endosomal recycling. However, in patients with hepatocellular carcinoma (HCC), the correlation among CMTM6, B7 family ligands, and CD8-positive cytotoxic T lymphocytes (CTLs), and the molecular function of CMTM6 in HCC have not been established. We performed immunohistochemistry to evaluate the relationships among CMTM6 expression, clinicopathological factors, B7 family ligands expression, and CTL infiltration in HCC samples. Moreover, we established CMTM6-knockout human HCC cell lines to evaluate the function of human CMTM6 in immune regulation and tumor viability. CMTM6 expression was positively associated with membrane B7 family ligands expression and CTL infiltration in HCC samples. High CMTM6 expression in HCC tissues was associated with the expression of the proliferation marker Ki-67 and shorter recurrence-free survival. In vitro analysis showed the downregulation of membrane B7 family ligands and proliferation potency in the CMTM6-knockout human HCC cell line. High membrane CMTM6 expression was associated with tumor recurrence and proliferation via the regulation of membranous B7 family ligands expression. Thus, CMTM6 might be a biomarker to predict the risk of HCC recurrence and a therapeutic target to suppress tumor growth and increase CTL activity.<br /> (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Aged
Aged, 80 and over
Biomarkers, Tumor metabolism
CD8-Positive T-Lymphocytes metabolism
Cell Line, Tumor
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
T-Lymphocytes, Cytotoxic metabolism
Carcinoma, Hepatocellular metabolism
Cell Membrane metabolism
Liver Neoplasms metabolism
MARVEL Domain-Containing Proteins metabolism
Myelin Proteins metabolism
Neoplasm Recurrence, Local metabolism
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 112
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 34080242
- Full Text :
- https://doi.org/10.1111/cas.15004